Bindsub 957..994

Subject index

a acoradiene absinthin 278 – acid-catalyzed cyclization to cedrene 236 – wormwood, isolation from Artemisia acorane–cedrane interconversion 237 absinthium L. 277 acoranes acetic acid – biogenetic relationship to zizaenes 255 – synthesis of 42, 921 acrylates – dianion of 301 – reduction of, with magnesium in methanol acetic acid side chain 442 – by alkylation of ketones 314 acrylic acids – mild hydrolysis of 698 – hydrogenation of 111 a-acetoxy ketone acyl anion equivalent – reduction of, with zinc 546 – generation of 862, 864 acetylation – in maytansine synthesis 857 – lipase-catalyzed 440 acyl anion synthons 188 (+)-acetylcephalotaxine 656 acylation acetyl-CoA 802 – of enamine with mixed anhydride 662 – in biosynthesis of cephalotaxine N-acylhomomeroquinene 534 esters 657 acyliminium cyclization 579 acetylenes acyloin condensation 661 – hydroboration of 379 – Ruhlman modification 662 acetylgynuramine 619 acylpyridines 3-acetyl-2-piperideine – hydrogenation of 771, 784 – acylation with methyl chloroformate 770 3-acylpyridines – by hydrogenation of 3-acetyl-pyridine 770 – hydrogenation to vinylogous amide 592 3-acetylpyridine – in general method of synthesis 195, 196, – hydrogenation of 592, 593, 770 593 – in indole alkaloid synthesis 195, 196, 771, 3-acylpyridinium salts 776 – acid-catalyzed cyclization of 593, 782 aconitine 530, 531, 847, 848 – in alkaloid synthesis 195, 196, 592

N-acyl vinylogous urea – of keto ester dianion 435 – attachment of, in palytoxin synthesis 901 1,4-alkylative dearomatization Adam’s catalyst 260, 375, 376, 397, 609, 626 – in cedrene synthesis 234 – hydrogenation of limonene 399 alkylative transposition aflatoxin 847 – of 1,3-carbonyl 664 aflatoxin B1 846 alkyl zinc b-agarofuran – addition to ketone 484 – synthesis 113 – in quassin synthesis 484 AIDS Alloferine 801 – treatment of 910 allyl ether ajmalicine 541, 542, 761 – reductive fission of 299 – in biosynthesis of indole alkaloids 762 allylic alcohols ajmaline 541, 542 – by reduction of malonates 316, 317 alcohol dehydrogenase – directed hydrogenation of 512 – in desymmetrization of meso diols 117 – from epoxides 485 alcyonin 5 – oxidation with MnO2 317 – structure revision 4 – reductive transposition of 488 aldehyde synthesis – by reduction of epoxy mesylates 317 – by hydrolysis of gem-dichloride to 782 allylic bromination 383 aldolase allylic carbamate displacement 741, 742 – in enzymatic aldol condensation 116 – suprafacial 742 aldol condensation 48, 292, 451, 453, 462, 664, – with lithiosilanes 741 766 allylic epoxidation 508 – asymmetric 55, 56 allylic oxidation 400, 472, 474, 476, 477, 509 – in damsin synthesis 305, 306 – chemoselective 310 – intramolecular 306, 583, 776 – of 1,4-diene to dienone 786 – in aspidospermidine synthesis 776 – of olefin to enone 556, 785 – in zizaene synthesis 261 – with 1,3-oxygen shift 352 – transition state model 57 – with retention of olefin regiochemistry alexine 639, 641 588 alizarin – with selenium dioxide 591 – synthesis 41, 42 p-allylnickel complex 319 alkaloid allyloxycarbonyl (ALOC) – origin of the word 527 – reduction of 182 alkaloids 5 allylsilane cyclization – chronology of isolation 528 – of acylimminium ion 627, 743 – general methods of synthesis 767 Amaryllidaceae constituents b-alkoxygenone synthesis 854 – bibliography 721 alkylation – biological acitivites of 689 – a vs. c control 168, 259, 260 – biosynthesis of 689, 691 – C vs. O control 168 – isolation 689 – C vs. O vs. N control 168 – structura 689 – of carbonyl compounds 167 – synthesis of ent-series 720 – of crotonates 167 ambrosin 278 a-alkylation americanolide 278 – of enone 511 amide reduction – of unsaturated ester 608 – via imino chloride 633 a-alkylation vs. c-alkylation amino cyclitols – of enones 259, 260 – synthesis of 155 Subject index 959 amino hydroxylation 58 – isolation from Cephalosporium aphidicola – asymmetric 641 Petch 449 aminoindanol – isolation from Nigrospora sphaerica 449 – from indane cis-diol 912 – synthesis of 104 (+)–(S)-amphetamine 529 – total synthesis, Corey 455 amphidinolide B 871 – total synthesis, Holton 105, 461 – synthesis of 869 – total synthesis, Ireland 456 (+)-amphidinolide W – total synthesis, McMurry 451 – synthesis of 869 – total synthesis, Trost 451 – revision of structure 871 D-arabinose amprenavir 911 – Kiliani–Fischer chain extension 24 – HIV-I protease inhibitor 910 – proof of stereochemistry 25 androsterone 208 arboflorine 849, 850 anionic cyclization arborescin 278, 295 – of alkoxides to enynes 293 arene–olefin cycloaddition 241, 389, anionic oxygenation 390, 420 – of benzylic carbon 540 – in retigeranic acid synthesis 400 anionic rearrangement – photochemical 372 – of imino esters 633 – in cedrene synthesis 239 a-anion synthons 188 aromadendrene 277, 278 anisole (–)-aromadendrene 325 – demethylation of 735 aromatic dihydroxylation 136 – oxidative cleavage 576, 579 aromatic substitution annopodine 574 – photostimulated 663 annotine 574 aromatin 278 annotinine 574 aromatization 854 – synthesis of 588 aspartyl protease – Wiesner’s synthesis 590 – inhibition of 911 [4+1] annulation 104, 406 aspidoalbine 760 – intramolecular of dienic aspidophytine 780 diazoketones 403 – total synthesis, Padwa 779 [3+2] annulation Aspidosperma alkaloids 761, 763, 764, 820 – in triquinane design 363 – approaches to 775 ansa compounds – general method of synthesis 769, 770, 772, – definition of 879 773, 776, 794 – history of 879 – structure elucidation 780 ansomytocins 851 – chemical interconversion of 764 antascomicin A 871 aspidospermidine 530, 760, 761, 764, 770, 772, – synthesis of 869 773, 776, 780, 794, 815 antascomicin B 871 – bibliography 826 1,4-anti elimination – conversion to vincadifformine 773 – of HBr, in diene synthesis 443 – disconnection analysis 765 aphidicolin 213, 449, 453, 454, 455, 463 – total synthesis, Aube 773 – asymmetric formal synthesis of 461 – total synthesis, Heathcock 775 – bibliography 464 – total synthesis, Kutney 775 – biogenetic-type synthesis 456 – total synthesis, Magnus 775 – biological activity of 449 – total synthesis, Schultz 786 – biomimetic approaches to synthesis 451 – total synthesis, Wenkert 767 – disconnection analysis 450 – total synthesis, Zard 775 960 Subject index

(–)-aspidospermidine – synthesis 244 – asymmetric synthesis of 786 – radical cascade of 243, 246 aspidospermine 531, 759, 760, 780, 921 azulene – bibliography 826 – from oil of chamomile 277 – comparison of Stork’s and Ban’s intermediates 767, 768 b – dehydrogenation with zinc dust 31 baccatin III 13, 499, 500 – disconnection analysis 765 – esterification of 507 – Emde degradation of 34 – symmetry-based design 151 – fragmentation of 32 Baeyer–Villiger reaction 118, 308, 309, 321, – Hofmann degradation of 34 485, 555, 556, 557, 560, 579, 705, 720 – isolation from Aspidosperma quebracho – asymmetric 59 blanco 764 – Hudrlik silicon-directed version 785, 786 – oxidation of 32 – in eburnamonine synthesis 786 – structure proof 23, 31 – in quassin synthesis 483 – total synthesis, Stork 765 baker’s yeast reduction – Xray structure 32 – of keto esters 639 Asteraceae families of plants barbatusol 488 – source of pyrrolizidine alkaloids 617 Barton–McCombie deoxygenation 246, 381, asymmetric oxidation 54, 110, 112, 117, 118 383, 388, 404, 409, 419 asymmetric reduction 110 Barton reaction 112 – of enones 667 Baylis–Hillman reaction 578 – with chiral oxazaborolidine catalysts 110, – of ethyl acrylate with 488, 667 m-methoxybenzaldehyde 577 atom economy 96, 727 Beckmann rearrangement 47, 48, 595, 800 – definition of 97 – in ibogamine synthesis 799 atom transposition – of dihydrocodeinone oxime 30 – in cyclic compounds 176 – Barton nitrone version 311, 313 atropine 529, 531 benzene atropoisomerism – chemical oxygenation of 119 – in vancomycin 873 – synthesis from acetylene 214 – in pancratistatin synthesis 698 – asymmetric dihydroxylation of 118 australine 639, 641 benzocyclobutane (+)-australine – cycloreversion 114 – total synthesis, Denmark 639 – in steroid synthesis 209 azabicyclo[3.3.0]octane 619 benzyl ether – disconnective strategies 620 – deprotection with BBr3 352 aza-Diels–Alder reaction N-benzoylmeroquinene 537 – in daphnilactone synthesis 609 o-benzyloxime 709 azadiene formation 609 benzyne alkylation aza–ene reaction – intramolecular 661 – of acylimminium ion 627 benzyne generation azaspiracid-1 6 – with sodium or potassium amide 663 – structure revision 5 Bergman cycloaromatization aza sugars – of ene-diyne subunit 873 – synthesis of 155 Beyermann–Grewe cyclization 737 azide–diene cycloaddition 636 bicyclic ketones N-aziridinyl imine – stability relationships in 177, 179, 180, – in radical cyclization 267 181, 279 Subject index 961 bicyclo[2.2.1]heptane bis(dihydroquinidino)–phthalazine – fragmentation of 308 – in asymmetric amino-hydroxylation 641 – in hydrazulene synthesis 307 1,2-bis(trimethylsiloxy)cyclobutane 663 bicyclo[2.2.2]octanone Bohlman–Wenkert bands – via a Diels–Alder reaction 560 – IR frequencies 576 bicyclo[2.2.2]octene – in structure elucidation of heterocycles – cleavage of 484 575 bicyclo[3.2.1]octanone bond-set analysis 130 – synthesis of 463 Boraginaceae families of plants bicyclo[3.2.1]oxaoctane – source of pyrrolizidine alkaloids 617 – in phorbol synthesis 470, 471 (–)-borneol 507, 517, 518 bicyclo[3.3.1]nonanone Bredt’s rule 588 – synthesis of 586 brevenal 874 bicyclo[3.3.0]octanes – biological activity 877 – energy differences 178 brevetoxin 850, 873, 921 bicyclo[5.3.0]decanones – biological activity 877 – energy differences 180, 279 brevetoxin A 874, 924 bicyclo[5.3.0]nonanones – bibliography 881 – energy differences 179 – from K. brevis 874 bicyclo[5.4.0]azaundecane ring system – total synthesis, Nicolaou 877 – conversion to isoguinuclidine 800 brevetoxin B 43, 46, 90, 874 bicyclo[6.3.0]undecanones – bibliography 881 – energy differences 181 – total synthesis, Kadota & Yamamoto 877 S-BINOL – total synthesis, Nakata 877 – in asymmetric Diels–Alder cycloaddition – total synthesis, Nicolaou 877 798 brevetoxins biocatalysis and directed evolution 59 – biological activities of 874 biogenetic cyclization – isolation 874 – of acoranes to cedrenes 231 brevity biogenetic relationship – in reaction design 95 – acoranes, cedranes, and zizaanes 235 brevity of execution biomimetic cyclizations – discussion of 89 – in acorane ring systems 236 bridgehead enone – in steroid synthesis 210 – synthesis of 586 – in synthesis of aphidicolin 455 – in lycopodine synthesis 585 biosynthesis of indole alkaloids a-bromination – Wenkert’s original hypthesis 761 – of amide 591 Birch reduction 50, 51, 260, 282, 305, 306, 456, bromination 457, 576, 579, 736, 737, 740, 854 – of ketone, acid catalyzed 735 – asymmetric 785, 786 N-bromination 536 – of anisole 259 a-bromoenone synthesis 667 – of gallic acid 853 b-bromoethyl benzene –ofp-methylanisole 218 – enzymatic dihydroxylation of 744 – of phenyl ethers as means of deprotection bromohydrin synthesis 546 280 o-bromotoluene Bischler–Napieralski reaction 47, 48, 50, 543, – lithiation of 372 547, 551, 553, 699, 711, 713, 736, 737, 761 Brown hydroboration 56 – in 7-deoxypancratistatin synthesis 702 brucine 528, 801 – via isocyanate 701 – isolation from Strychnos ignatii 800 962 Subject index

– isolation from Strychnos nux vomica 800 (–)-camphor 504, 507, 517, 518 Buchner–Curtius–Schlotterbeck reaction 263 camphorsulfonic acids 262 – in khusimone synthesis 262 (–)-L-10-camphorsulfonic acid 262 bulgarsenine 617, 618 (camphorsulfonyl)oxaziradine 903 bulnesene 280 camptothecin 845 – disconnection analysis 281 Cannizzaro reaction 48 a-bulnesene 283, 286, 287, 288, 291 capnellene 362, 363, 386, 389 – total synthesis, Heathcock 286 capsaicin 529 – total synthesis, Mehta 290 (CAPS) routine – total synthesis, Piers 281 – in CAD of synthesis 133 b-bulnesene 287 caracurine 801 – total synthesis, Oppolzer 290 carbamate hydrolysis 784, 811, 857 – total synthesis, Sammes 293 carbamate synthesis 694 bulnesol 213, 278, 282, 285, 286, 287, 288, 324 carbenoid – total synthesis, Heathcock 286, 287 – insertion into C–H bonds 111, 745 – total synthesis, Marshall 280 1-carbethoxy-3-oxopyrrolizidine – total synthesis, Yoshikoshi 284 – reduction of 627 Burgess dehydration 505 carbohydrate Burgess reagent 240, 242, 298, 299, 505, 507, – as source of asymmetry 855 706 carbohydrate design – for olefin synthesis 708 – topology-based 143 t-butanol 42 carbohydrate synthesis butenolide – aldolase-mediated 116 – by selenoxide elimination 316 – from aromatic compounds 137 – from furans 320 – symmetry-based design 136 – synthesis from keto acids 309 b-carboline alkaloids 559 n-butyl lithium borohydride b-carbolines – enone reduction with 856 – mechanistic options for equilibration of 1-butyne 552 – Suzuki cross-coupling with vinyl bromide carbomethoxydihydrocleavamine 794 798 carbonate pyrolysis 283 carbonate synthesis 504, 505 c carbon efficiency CAD technology 133 – discussion of 96 caffeine 528 carbonyl group I calicheamicin c1 43, 46, 847, 848, 872 – 1,3-transposition 311 C-alkylation N-carboxylic acids, vinylogous connectivity – of 1,3-diketone 487 798 calystegine Cargill rearrangement 411 – chemoenzymatic synthesis of 117 – in isocomene synthesis 371 CAMEO programs 130 – migratory aptitudes 372 camphor 42, 502, 921 carotol 278 – as chirality source in taxane – isolation from Daucus carota L. 277 synthesis 517 carvone 209, 399 – as chiral starting material in total – Favorskii rearrangement 301 syntheses 271 (–)-carvone 301 – synthesis of 41, 207 (R)-(–)-carvone 402 (+)-camphor 504, 517, 518 cascade – oxidation to camphorquinone 516 – definition of 121 Subject index 963

– reactions 101 – bibliography 683 cascade cyclizations – disconnection analysis 659 – in daphnilactone synthesis 609 – esterification of 671 – of diazo carbonyl compounds, Rh(II)- – esterification of, with dihydropyranic acid catalyzed 819 673 – of hydroxy epoxides 877 – isolation and structure 655 – in perovskone synthesis 489 – synthetic strategies 669, 670 – in vindoline synthesis 780 – total synthesis, Mariano 663 castanospermine 847, 848 – total synthesis, Semmelhack 662 catalysis 930 – total synthesis, Tietze 666 catalytic oxidation – total synthesis, Weinreb 659 – Sharpless–Katsuki expoxidation 110 (–)-cephalotaxine 666, 670 catechol cephalotaxine esters – cyclic sulfate protection 734 – biological activities 655 catechol borane 739 – synthesis of 671 catharanthine 788, 789 cephalotaxinone 656, 663 cationic cyclization Cephalotaxus alkaloids – biomimetic, in cedrene synthesis 234 – biosynthesis of 655, 658 – in daphnilactone synthesis 609 – from C. drupacea 655 – in biosynthesis of indole alkaloids 761 – from C. fortunei 655 a-cation synthons 188 – from C. harringtonia 655 cedrene 41, 43, 213, 229, 230, 299, 316, 321, Chan rearrangement 504 372, 804, 909, 921, 922, 924 – in taxol synthesis 506 – bibliography 251 chaparrinone 479, 481 – biosynthesis 231 Chatterjee’s ketone 370, 374, 377, 378, – disconnection analysis 230 379, 410 – from Juniperus species 229 chemical biology – structure determination 229 – relation to organic synthesis 922 – synthesis of 107, 114 chemical literature – total synthesis, Corey 231, 236 – integrity of 923 – total synthesis, Fallis 236 chemical synthesis – total synthesis, Kerr 243 – purpose of 850 – total synthesis, Kim 243 chemoselectivity 183, 185 – total synthesis, Lawton 235 – definition and principles of 182, 199 – total synthesis, Naegeli & Kaiser 236 – in deprotection 184 – total synthesis, Rigby 240 – in hydrolysis 184 – total synthesis, Stork 230 – in oxidation 184 – total synthesis, Wender 239 chemospecificity a-cedrene – definition of 199 – by dehydration of cedrol 229 chiral auxiliary 99 – synthesis of 235 – in indinavir synthesis 99, 912, 914 b-cedrene 229 – in indolealkaloid synthesis 776 – synthesis of 235 chiral benzamides cedrol 35, 230, 231 – Birch reduction of 786 – dehydration of 239 chiral ferrocenyl derivative – synthesis of 235 – in vindoline synthesis 776 cephalotaxidine 655, 657 D-chiro-inositol 715 cephalotaxinamide 656 – structural relationship to pancratistatin cephalotaxine 529, 531, 656, 666, 670 149, 696

L-chiro-inositol cleavamine 788, 789 – structural relationship to pancratistatin Clemmensen reduction 51, 290 149, 696 codeine 530, 728, 730 chiron 157 – bibliography 753 – definition of 133 – demethylation of, to morphine 26, 733, CHIRON program 133, 143 736 chloroenones – history 727 – reduction of with zinc 581 (–)-codeine 739 a-chloroenone synthesis 854 codeine methiodide 30 chlorophyl 807 codeinone 28, 728, 730 cholestanone 514 – oxidative degradation of 28 cholesterol 208 colchicine 528, 529, 846 chromium–nickel coupling 902 – synthesis of 847 – in palytoxin synthesis 895, 898, 899 – tubulin-binding agent 847 – of vinyl iodide (triflate)and aldehyde 896, (–)-colchicine 898, 899 – synthesis of 847 – proposed mechanism 898 Collins oxidation 316, 482, 484, 861, 864 chrysanthenone 510 Collman reagent 452 Chugaev reaction – for metal-mediated CO insertion 454 – xanthate pyrolysis 260 combinatorial chemistry 59 ciguatoxin 875 commutative principles – bibliography 881 – in synthetic design 154 – biological activity 877 compactin 213, 431, 432, 845 – isolation from dinoflagellate – bibliography 445 Gambierdiscus toxicus 876 – biological activities 431 – isolation from morayeels 875 – chemoenzymatic synthesis 432 – structure elucidation 875 – disconnection analysis 433 cinchonine 528 – isolation from Penicillium cinnamyloxycarbonyl group (COC) brevicompactum 431 – reduction of 182 – isolation from Penicillium citrinum 431 citation index – synthesis by fermentation 443 – of organic chemists 12 – total synthesis, Funk 436 cladantholide 278 – total synthesis, Grieco 436 (+)-cladantholide 303 – total synthesis, Hagiwara 440 Claisen condensations 48 – total synthesis, Sih 432 – in damsin synthesis 305 complex cycloadditions and annulations 59 Claisen rearrangement 51, 260, 293, 295, 380, complex macrocycles 871, 872 454, 456, 457, 479, 666, 696, 699, 700, 745 compressanolide 299 – in aphidicolin synthesis 451 computer-assisted design (CAD) 87, 129, 130 – in compactin synthesis 443 conduramine 712, 713 – in epi-b-bulnesene synthesis 295 conduritol – of allyl phenol ether 259 – chemoenzymatic synthesis from arene – of glycinate ester 753 diols 118 – ortho-ester variant 374, 375, 377, 385 confertin 213, 278, 280, 304, 316, 321, 330, 333 – Overman imidate version 695, 696 – disconnection analysis 315 – regiochemical preference for olefins vs. – topographical similarities with decaline acetylenes 377 lactones 314 – regioselectivity for olefin substitution 379, – total synthesis, Marshall 315 384 – total synthesis, Quinkert 321 Subject index 965

– total synthesis, Schlessinger 311 Crabtree catalyst 390 – total synthesis, Schultz 318 – hydrogenation with 389, 510 – total synthesis, Semmelhack 318 crinine 689, 690, 691 – total synthesis, Wender 309 crinipellin A 362 conformational analysis CRIXIVAN 915 – of taxane ring system 506 crooksidine 763 Conia–Dauben modification – from Haplophyton crooksii 761 – of the Wittig reaction 256, 261, 298, 299, cross-coupling 301, 375, 376, 380, 382, 413 – of benzylic iodide with mixed cuprate 853 Conia-type ene reaction cuprate addition 352 – in isocomene synthesis 365 – asymmetric 321, 322 coniine 528, 531 – to enones 318 (R)-coniine 529 Curtius rearrangement 48, 701, 713 conjugate addition 583 – in pancratistatin synthesis 699 – in retigeranic acid synthesis 399 – with diphenyl-phosphorazidate (DPPA) – 1,6-, Lewis acid catalyzed, intramolecular 705 486, 487 cyanohydrin synthesis 238 – of dienolate to enone 264, 265 – high pressure conditions 398, 399 – regioselectivity of 1,2- vs. 1,4- 167 cyclic carbamate connectivity analysis 129, 130 – synthesis of 859, 860, 866 connectivity relationships cyclic carbonate – in carbohydrates 144 – cleavage of 505, 512 – in triquinane terpenes 144 – synthesis of 505, 508, 512 consecutive reactions 101 cyclic ethers – definition of 121 – ring expansion of 877 consonant–dissonant relationships 186, 187 cyclic sulfate convergent assembly – opening of 701, 869 – of palytoxin 896 – synthesis of 477, 701 convergent synthesis 99 cyclitols Cope rearrangement 51, 310, 381, 557, 611 – chemoenzymatic synthesis of 117 –ofcis-divinylcyclobutane 207 cyclization – of divinylcyclopropane 60, 309, 310 – of 3-acetyl pyridine, in eburnamonine copper chromite synthesis 783 – for reductive coupling 734 – sequential, in vindoline synthesis 776 – reductive coupling of nitriles 575 [2+2] cycloaddition 218, 263, 289, 292, 470 Corey–Chaykovski epoxidation 222 – in estafiatin synthesis 218 Corey–Fuchs reaction 709, 710 – in ingenol synthesis 470 Corey–House reaction 853, 859 – in perovskone synthesis 487 – cuprate alkylation 58 – intramolecular, in ingenol synthesis 476 – aryl–alkyl coupling (via aryl cuprate) 861 – in zizaene synthesis 263 Corey iodolactonization 347, 694, 701 – of allene 585 – in vernolepin synthesis 346 [3+2] cycloaddition Corey lactone 42, 44 – of oxonium ylide 780 coriolin 362, 363, 386, 418 [4+2] cycloaddition 300, 391, 402, 606, 483, 666, – isolation from Basidiomycete Coriolus 776, 810 consors 361 – in quassin synthesis 483 – synthesis of 389 – intramolecular, exo transition state 810 coronaridine 794, 795, 798 – intramolecular, of acylnitroso compounds cortisone 208, 807 666 966 Subject index

– in tabersonine synthesis 776 para-cyclophane – in vindoline synthesis 776 – in strychnine synthesis 810 – in zizaene synthesis 267 para-cyclophane synthesis 811 – Lewis acid-catalyzed 300 cyclopropanation 477, 770 [4+3] cycloaddition – catalytic enantioselective 111 – of furan and oxyallyl species 475 – copper-catalyzed 375 [5+2] cycloaddition – intramolecular 379, 404, 631, 632 – in phorbol synthesis 470 – intramolecular, of 1,3-dienes, 404 – metal-catalyzed 329 – intramolecular, of b,b-disubstituted – of pyrylium 472, 475 arcylates 376 [6+2] cycloaddition 242 – of enamide 771 – intramolecular, Cr(0) promoted 240, 250 – of enol ether 767, 784 cycloadditions – of enones, via a-bromodienolate addition – in hydroazulene synthesis 280 408 – intramolecular, 1,3-diyl 387 – with dimethylsulfonium ylide 473 – intramolecular oxime–olefin 627 – with diphenylisopropylsulfonium ylide – in vindoline synthesis 780 475 – of cyclopentadiene and cyclopropanes methylenecyclopropane 268 – nucleophilic opening 628 – cyclobutylcarbinyl rearrangement cyclopropylcarbinyl rearrangement 189, 241, – in isocomene synthesis 371 243, 267, 317, 390, 402, 738, 771, 784 – of oxidopyrylium, in bulnesene synthesis – in cedrene synthesis 240 294 – in eburnamonine synthesis 783 cyclocoloreneone 277, 278 – in indole alkaloid synthesis 769 cycloheptane annulation – in juvenile hormone synthesis 223 – intramolecular 319 – in retigeranic acid synthesis 400 cycloheptenone annulation 320 – in ring expansion 330 cyclohexa-1,3-dione-5-carboxylic acid – in steroid synthesis 209 – from gallic acid by Birch reduction 853 – in terpene synthesis 193 cyclohexanone annulation – of oxa and azacyclopropyl esters 783 – via carbonyl insertion 454 – zinc bromide-mediated 736 cyclohexanone monooxygenase 59 cyclopropyl imine – in enzymatic Baeyer–Villiger – generation of, in strychnine reaction 118 synthesis 810 cyclohexenone cyclopropylimine–pyrroline rearrangement – synthesis from 2-methyl pyridine 176 – acid-catalyzed 635 cyclopentadione annulation 664 – discovery of 635 [3+2] cyclopentene annulation 377 – in strychnine synthesis 809 [4+1] cyclopentene annulation 139, 374, 375, cyclopropyl indolenine 377, 382, 385 – from tryptophyl bromide 823 – intramolecular 385,404 cyclopropylketone-olefin cyclization 237 – retrosynthetic analysis of 139 cyclopropylphosphonium salt cyclopentene annulation – nucleophilic opening of 635 – [4+1] and [3+2] disconnections for 407 cyclotrimerization – [3+2] intermolecular 408 – in steroid synthesis 209, 211 – via oxaspirocyclopentane and cyguatoxin CTX3C vinylcyclopropane rearrangement 452 – total synthesis, Hirama 877 cyclopentene carboxylate cylindricine 5 – kinetic alkylation of 606 cytochalasin 845 Subject index 967 cytochalasin D – biological activities 603 – synthesis of 176 – biosynthetic origin 603 cytochrome P-450 – D. yunnanense 603 – in morphine biosynthesis 728 – from D. teijsmanii 603 – from D. macropodum 603 d – pharmacology of 603 (+)-dactylolide 871 – representative members 604 – synthesis of 869 – structure elucidation 603 damsin 213, 278, 280, 304, 309, 314, 321 – suggested biosynthesis of 605 – disconnection analysis 305 Darzens glycidic ester 48 – topographical similarities with decaline daucol 278 lactones 314 – isolation from Daucus carota L. 277 – total synthesis, Grieco 307 daunomycinone 846, 847 – total synthesis, Kretchmer 304 Davis a-hydroxylation 504, 505, 506, 511, 663, – total synthesis, Schlessinger 311 664 damsinic acid 213, 278, 280, 304, 311, 330 – with canphorsulfonyl oxaziridine 504, 506 – disconnection analysis 305 Davis’s oxaziridine reagent – total synthesis, Wender 309 – in palytoxin synthesis 901, 903 Danishefsky diene 10-deacetyl baccatin III 500 – Diels–Alder reaction of 456 cis-decaline synthesis 347 – in compactin synthesis 443 decarbomethoxylation – in vernolepin synthesis 346 – of methyl carbamates 623 Danishefsky lactone 696 decarboxylation – recyclization to amide 695 – base-catalzyed 304 daphmanidin E 603, 604 –ofb-keto ester 505 daphnane decarboxylative dehydration 400 – in Euphorbiaceae and Thymalaeaceae degenerate condensation families 469 – in lycopodine synthesis 108 – skeleton ring system 470 degenerate operations daphnetoxin 470 – definition of 107 – from the bark of Daphne mezereum – in pancratistatin synthesis 109 (Thymelaeaceae) 470 – in cedrene synthesis 107 daphnilactone 43, 531, 922 dehalogenation daphnilactone A 45, 530, 603, 611 – radical 667 – biosynthesis of 606 dehydroaspidospermidine 772 – disconnection analysis 607 – reduction to aspidospermidine 770 – total synthesis, Heathcock 606 – reductive cleavage to daphnilactone B 603 quebrachamine 770 daphnilongeranin 603 dehydrobromination daphnilongeranin A 603, 604 – in compactin synthesis 437 daphnilongeranin C 604 dehydrokessane 278, 289, 290 – from Daphniphyllum longeracemosum – total synthesis, Liu 288 603 dehydropreakuamicine daphnilongeranin D 604 – in strychnine biosynthesis 802 daphniphyllate dehydroprogesterone – synthesis 106 – synthesis 209 daphniphylline 603, 604 dehydrostrychninone Daphniphyllum alkaloids 603, 613 – intermediates in strychnine degradation – bibliography 614 807 968 Subject index dehydrotubifoline – of dimethyl 3-methyl glutarate with pig- – synthesis of 810 liver-esterase 399 delphinine 531 – of diols 185 demercuration – of meso compounds 89 – by RHgOAc to RHgCl exchange 855 detosylation 805 demethylation diallylbisnortoxiferine dichloride 801 – of methyl ethers 345 diazo ester ring expansion 282 – of methyl ether with BBr3 439 diazonamide A 6 demethylation conditions – structure revision 5 – of pancratistatin C-7 methoxy group 713 diazo transfer reaction 630, 631, 632 demethylcephalotaxinone 656, 662 DIBAL-H reduction 555 6-demethyl-6-deoxytetracycline 846 m-dibromobenzene demethylneodrupacine 655, 656 – enzymatic oxidation of 709 demethylcephalotaxine 656 – whole-cell fermentation of 712 deoxydamsin 304, 309 dibromoethane 770 6-deoxyerythronolide B b-dicarbonyl compounds – formal total synthesis of 867 – dianion generation from 170 deoxygenation – hydrogenation of 111 – of alcohols, with N,N-dimethyl 1,4-dicarbonyl compounds phosphoroamidate 290 – synthesis of 767, 769 deoxyharringtonine didehydrosecodine 761, 763 – synthesis of 657, 671 – in biosynthesis of indole alkaloids 762 4,5-deoxymaysine – in tabersonine synthesis 776 – synthesis of 859 – intermediate in indole alkaloid deoxynojirimycin biosynthesis 763 – synthesis of 116 Dieckmann condensation 48, 505, 507, 592, 7-deoxypancratistatin 102, 149, 151, 689, 690, 627, 628, 630, 804, 805 702, 709, 714, 716, 717 – in damsin synthesis 305 – synthetic strategies 704 Diels–Alder cyclization – total synthesis, Hudlicky 704 – biomimetic, of didehydrosecodine 775 – total synthesis, Keck 704 Diels–Alder cycloaddition 238, 386, 395, 406, – total synthesis, Padwa 704 420, 438, 439, 456, 546, 556, 694, 711, 733, 791, – total synthesis, Plumet 704 810, 873 deoxyquinine 532, 537, 538, 539 – asymmetric 799 deprotective operations 190 – in biosynthesis of indole alkaloids 761 desacetoxy-4-oxo-6,7-dihydrovindorosine 779 – in ibogamine synthesis 799 design-dimensional analysis – in quassin synthesis 481 – in synthetic planning 129 – in retigeranic acid synthesis 394 – principles and issues of 129 – intramolecular 810, 872 Dess–Martin oxidation 245, 477, 478, 512 – intramolecular, in strychnine synthesis desulfurization 232, 438, 460, 462, 858, 860, 869 809 – of thioenol ether 806 – intramolecular, of p-cyclophane 804 – of thioketal 231, 258, 771 – intramolecular, of 2-pyrone 554 – of thioketal with mercuric chloride 859 – Lewis acid catalyzed 436, 437, 481 – of thiophenyl ethers 459 – of acylnitroso compounds 705, 709, 711, – with Raney nickel 780, 807 713 desymmetrization – of a pyrone 552 – by esterase 707 – of cyclopentadienes 555 – of acetates 185 – of imino ester 557 Subject index 969

– of pentadienoic acid 544 1,2-dihydropyridine – of 1,2-pyridazine with indole 810 – Diels–Alder adducts with methyl-vinyl – of quinone 544 ketone 790 – of trans-b-ocimene 486 3,4-dihydroxybenzoic acid 39 – of 3-vinyl indole 786 dihydroxyheliotridane 636, 637, 638 – with Danishefsky diene 347 – total synthesis, Hudlicky 635 Diels–Alder reaction 51, 343, 388, 395, 399, dihydroxylation 58 405, 408, 461, 482, 487, 488, 507, 543, 595, 605, – of arenes 56, 59, 638 606, 693, 705, 713, 734, 751, 752, 921 2,6-dihydroxynaphthalene 733 – asymmetric in synthesis of ibogamine 798 3,4-dihydroxyphenanthrene 38, 39 – biomimetic in indole alkaloid synthesis dihydroxyphenanthrene 779 – product of morphine degradation 27 – in compactin synthesis 436, 443 – synthesis of 27 – in taxol synthesis 508 diimide reduction 268, 387, 438 – intramolecular 401 diketocoriolin B 414 – intramolecular in strychnine synthesis a-diketone 804 – methylation of 485 – intramolecularly tethered by boronic acid 1,3-diketones 508 – by Kuwajima’s aldol-pinacol – intramolecular of pyridazine 811 method 665 – in vernolepin synthesis 346 – reduction of 233 – inverse electron demand 810 1,4-diketones – in vindoline synthesis 776 – synthesis of, by isomerization of – Lewis acid catalyzed 484 c-hydroxyenones 773 – of a vinyl allene 443 dimeric indole alkaloids – of azadiene in daphnilactone synthesis – synthesis of 531 607 3,3-dimethyl acrylate – of dihydropyridine 557 – dienolate anion of 264 – of nitroacrylate with furan 436 1,2-dione synthesis 661 [4+1] diene–carbene annulation 249 diosphenol formation 482 – in triquinane design 363 dioxenone synthesis 476 1,3-diene synthesis diphenylphosphoryl azide – by dehydrobromination 442 – in Curtius rearrangement 699 – regioselective, in compactin synthesis 436 [3+2] dipolar cycloaddition 622, 624 – in palytoxin synthesis 901 – of oxonium ylide 595 dienic ester synthesis – of pyrroline-oxide 620 – by vinylogous Reformatsky reaction 377 1,3-dipolar cycloaddition dienolate addition to enones 408 – in supinidine synthesis 627 [3+2] dienolate–enone annulation directed evolution 59 – in triquinane design 363 directed o-metalation 58, 623, 694, 696, 697 dienone synthesis – functional proximity effects 113 – by oxidation of 1,4-dienes 310 – history of 122 dihydrocatharanthine 794, 798 – of aromatic compounds 112 dihydrocleavamine 794, 795, 797 discodermolide 91, 847, 849 – by reduction of the quaternary salt 797 – total synthesis 90 dihydrocodeinone 739, 741 disodium tetracarbonylferrate – demethylation of 736 – CO insertion with 452 dihydrocompactin 432 dissolved metal reduction 182, 373 dihydroeudesmol 288 – of enones 231 970 Subject index

– of epoxy ketones 298 electrochemical reduction 182 dissonance 188, 189 eleutherobin 849 – in synthesis 187 elimination diterpene alkaloids 847 – in olefin synthesis 297 – general methods of synthesis for 531 Emde degradation dithiane synthesis 855 – of aspidospermine 32, 33 dithiane-type anion emetine 528 – generation of, in maytansine synthesis 863 enamide cyclization 660 dithio ester synthesis 861, 864 enantiodivergence divinylcyclopropane – control of 111 – photolysis of 310 enantiodivergent design 146 – thermolysis of 310 enantiodivergent synthesis divinylcyclopropane rearrangement 102, 329 – of bicyclo[3.2.1]octene building blocks 350 1,3-diyl cycloaddition – of carbohydrates 146 – intramolecular 386 – of cyclitols 146 dodecahedrane 43, 45, 847, 848 enantiomeric switch dolastatin 19 – in pinitol design 148 – revision of structure 871 7-endo-trig cyclization – synthesis of 869 – in estafiatin synthesis 303 domino reactions ene-diyne antibiotics – definition 101, 121 – biological activity 873 double diastereoselection – total synthesis 873 – in maytansine synthesis 858 ene reaction 487 4,5-doxymaytansinol 9-O-methyl ether 859 – acid-catalyzed 259 drupacine 655, 656, 676 – anionic variant of 262 – in isocomene synthesis 365 e – in pyrolysis of vinyl aziridines 623 eburnamines 781 – intramolecular 262, 366, 487 eburnamonine 530, 531, 560, 760, 761, 786 – intramolecular, in khusimone synthesis – asymmetric synthesis of 786 264 – bibliography 826 – in triquinane design 363 – disconnection analysis 781 – in zizaene synthesis 261 – isolation of, from Hunteria eburnea – of singlet oxygen 457 Pichon 780 enolate generation – synthetic strategies for 787 – in trans- and cis-fused – total synthesis, Bartlett and Taylor 781 decalin-2-ones 170 – total synthesis, Ghosh 787 enone – total synthesis, Grieco 787 – kinetic alkylation of 371 – total synthesis, Schultz 786 – lead tetraacetate cleavage of 356 – total synthesis, Wenkert 782, 783 – oxidative cleavage of 347 Eburnea alkaloids enone synthesis – general synthetic strategy 769 – by bromination-dehydrobromination Eburnea skeleton 763 sequence 320 – chemical interconversion of 764 – by Pd-catalyzed oxidation of silyl enol – general approach to, Wenkert 195, 770 ethers 313, 458, 460 effective mass yield (EMY) – from 1,3-diketone 578 – definition of 97 – from vinylogous acid chloride 582, 583 efficiency factors enrichment – current definitions 96, 97 – of mixtures 896 Subject index 971 enyne cyclization epoxidation of allylic alcohol – zirconocene mediated 473, 475 – with t-butyl peroxide and enyne metathesis 873 oxyvanadium(IV)bis(acetylacetone) 859 enzymatic acylation 185 epoxide synthesis 707 enzymatic Baeyer–Villiger oxidation 56, 59 – from ketones, with dimethyl sulfonium enzymatic desymmetrization methylide 262 – of meso compounds 117, 148 – from diols 438 – of diketones 434 epoxy alcohol fragmentation enzymatic dihydroxylation 711 – in synthesis of taxanes 504, 506, 511 – of arenes 118, 697 – in taxol synthesis 511 enzymatic hydrolysis 185 – Lewis acid catalyzed 503 – of butyryl ester 705 a,b-epoxyamide synthesis enzymatic resolution – in annotinine synthesis 592 – of alcohols, via lipase-catalyzed epoxy ketones acetylation 441 – hydrazine reduction of 313 – of epoxy butyrates 707 – reduction of 344 epialexine equatorial reduction – total synthesis, Han 640 – stereocontrol, with L-selectride 459 (+)-1-epiaustraline equilenin 14, 41, 43, 208, 921 – total synthesis, Denmark 639 – total synthesis 7 (–)-7-epiaustraline equilibration of aspidospermidines – total synthesis, Denmark 639 – via retro-Mannich reaction 772 epiaustraline equilibrium – total synthesis, Denmark 639 – of aspidospermine and quebrachamine – total synthesis, Han 640 767 epi-b-bulnesene erythromycin 845 – total synthesis, Ovaska 293 – control of stereochemistry of the seco- – total synthesis, Sammes 293 acid 869 epiibogamine 792 – derivatives of 867 epiisocomene 377, 378, 379 – synthesis by fermentation 867 – total synthesis, Hudlicky 377 – Woodward’s iterative strategy 868 b-epiisocomene 378, 379, 380 erythromycin A 807, 868 – ozonolysis of 380 – total synthesis of 867 – total synthesis, Hudlicky 377 erythromycin B 868 epikessane 290 – formal total synthesis of 867 12-epi-lycopodine 574 erythronolide A 868 – synthesis of 585 erythronolide B 42, 44, 868 – Wiesner’s synthesis of 587, 589 D-erythrose 638 epimerization L-erythrose 638 – of C-14 in morphine 735 erythrose epizizaene 256, 261 – synthesis from chlorobenzene 639 – total synthesis, Wiesner 257 L-erythruronolactone 149, 638 epizizanoic acid 256 – synthesis from chlorobenzene 639 – synthesis from khusimone 262, 264 Eschenmoser fragmentation 176, 312, 314 – total synthesis, Yoshikoshi 256 Eschenmoser salt 310, 311, 512, 513 epoxidation –ina-methylene lactone synthesis 300, 301, – hydroxyl-directed 503 302, 349 – of enones, with t-butyl hydroperoxide Eschenmoser thioimino ester rearrangement 343 633 972 Subject index estafiatin 213, 278, 280, 295, 303 Fetizon oxidation 351, 352, 439, 440, 482 – disconnection analysis 296 filifolone 249 – total synthesis, Crabb 296 Finkelstein reaction 231, 232, 268, 308, 309, – total synthesis, Lee 301 736, 738, 914 – total synthesis, Rigby 299 – in aspidospermidine – total synthesis, Vandewalle 297 synthesis 776 estrone 208, 211, 357 Fischer indole synthesis 47, 48, 543, 761, 765, – synthesis 209, 211 766, 773, 800, 805 ether hydrolysis – in ibogamine synthesis 799 – via exchange with iPrSH 860 – regioselectivity with unsymmetrical ethoxy ethyl protecting group 861, 864 ketones 767 ethyl aluminum dichloride five-membered ring annulations – as Lewis acid catalyst, in Diels–Alder – carbocyclic 140 reaction 436 – heterocyclic 140 ethyl 4-bromocrotonate 627 flash vacuum pyrolysis 379, 384, 385, 408, 452, ethyl diazoacetate 624, 636 – cyclopropanation with 770 – of vinylaziridines 637 ethyl dithioacetate – of vinylcyclopropanes 376, 404, 451 – in maytansine synthesis 863 flow pyrolysis 454 eudesmol 288 formic-acid-catalyzed cyclization eurypamide A 5 – in cedrene synthesis 235 – structure revision 4 forskolin 432 E value/EQ value – biological activities 431 – definition of 97 FR-900848 848 Evans chiral auxiliary fragmentation – in asymmetric aldol reaction 472 – of cyclic ether, Lewis acid-catalyzed 609, – in indinavir synthesis 912 611 Evans chiral auxilliary fredericamycin 5-exo-trig cyclization – synthesis of 665 – in estafiatin synthesis 303 1,4-free radical addition experimental space 129 – of thiophenol to 1,3-dienes 389 extrapolations Friedel–Crafts acylation 306, 318, 321 – analysis of 139 – in damsin synthesis 304 – in neat polyphosphoric acid 770 f – of indoles 771 Fabaceae families of plants Friedel–Crafts alkylation 321, 486, 666, 670, – source of pyrrolizidine alkaloids 617 736 Family of Isomeric Ensembles of Molecules fructose 42 (FIEM) 142 fulvene synthesis 387 – definition of 141 functional connectivity 133 farnesol 207 functional group compatibility Favorskii rearrangement 47, 48, 397, 402, 403, – principles of 182, 186 404, 408 functional group transposition 172 – in estafiatin synthesis 302 – of carvone derivatives 301 g – of pulegone dibromide 394 Gabriel amine synthesis 630, 632 fawcettimine 574 – phase transfer conditions 629, 631 Ferrier rearrangement 136, 143 galanthamine 529, 689, 690 ferruginol 349, 357 gambieric acid A 875 Subject index 973 gambieric acids Grob fragmentation 258, 289, 321, 323 – biological activity 877 – in juvenile hormone – isolation from dinoflagellate synthesis 219, 221 Gambierdiscus toxicus 876 Grubbs metathesis 53, 479 gambierol 875 – in pancratistatin synthesis 699 – bibliography 881 Grubbs olefin metathesis 700, 877 – biological activity 877 – as complement to lactonization procedure – isolation from dinoflagellate 869 Gambierdiscus toxicus 876 Grubbs–Schrock metathesis 56, 867 – total synthesis, Rainier 877 guaianes 280 – total synthesis, Sasaki 877 guaianolides 295 – total synthesis, Yamamoto 877 guaiol 213, 278, 280, 287 gascardic acid – isolation from Guaiacum officinale 277 – synthesis of 207 guanacastepenes 849 geissoschizine 761 – activities against Staphylococus aureus – in biosynthesis of indole alkaloids 762, 847 802 – isolation from fungi 323 geraniol 209 D-gulonolactone geraniol pyrophosphate 759 – in narciclasine synthesis 709 – in biosynthesis of indole alkaloids 762 gymnocin A gibberellic acid 133, 846, 847 – bibliography 881 Gilman reagent 853, 856 – biological activity 877 – in Corey–House reaction 854 – from Karenia mikimoto 878 ginkgolide B 846, 847 – from Gymnodinium breve glaucarubinone 479 – taxonomic history 879 glaucarubolone 479, 481 – total synthesis, Sasaki 877 D-glucose 42, 921 gymnocin B 878 – structure proof of 23 – proof of stereochemistry 25 h – synthesis 41 hackelidine 618 (S)-glycidyl tosylate – from Hackelia californica (Gray) – in indinavir synthesis 912 Johnston 617 glycol cleavage hainanensine 656 – with periodate 454 halichlorine 847, 848 glycosidase inhibitors Haller–Bauer reaction – biocatalytic synthesis 116 – of bicyclo[2.2.1]heptenones 557 grandisol b-haloether – synthesis of 207, 208 – reduction of, with zinc 546 grantaline 618 – reductive cleavage, with zinc 473 – from Crotalaria virgulata 617 hard-soft symmetry 168 graph theory 87, 129, 130 harringtonine 655, 657 green chemistry 8, 9, 930 – synthesis of 671 – principles of 16 hastanecine 636, 637, 638 Grewe cyclization 736, 737 – total synthesis, Hudlicky 635 – in morphine synthesis 731 Heck coupling 53 Grieco olefination 366, 395, 400 Heck reaction 56, 513, 741, 745, 810 – via selenoxide elimination 366 – asymmetric 666, 668 Grignard reagent 666 – in approaches to morphine skeleton – coupling to alkenes 58 744 974 Subject index

– intramolecular 709, 713, 739, 741, 743 Holton–Ojima protocol – intramolecular in strychnine synthesis – for baccatin III esterification 510 804, 809 homocamphor 36, 325 helenalin 278, 311 homogeranyl iodide 606 – topographical similarities with decaline homoharringtonine 657, 676 lactones 314 – antitumor activities 655 helifoline 617, 618 – asymmetric synthesis of 671 heliotridane alkaloids 157 – isolation and structure 655 heliotridine 617, 618, 637, 638 – synthesis by partial esterification 671, 672, – total synthesis, Hudlicky 635 674 Helquist [3+2] annulation 369, 394, 397 – total synthesis, Hudlicky 671 – in triquinane design 363 homomeroquinene 532, 534, 537 hemibrevetoxin 881 – syntheses 539 – bibliography 881 homosecodaphniphyllate – total synthesis, Nicolaou 877 – total synthesis of 606 hemibrevitoxin B 874 homospermidine 619 Henry reaction 713 Horner–Wadsworth–Emmons olefination 53, heroin 267, 268, 311, 319, 387, 408, 442, 700, 857, 858, – illicit market 727 859, 861, 902 N-heterocyclic carbenes 110 – intramolecular 313 hetero Diels–Alder reaction 457 – in vincamine synthesis 788 hexahydrojulodinine – of the final two subunits, of palytoxin – stereoisomers of 576 905 hexoses – with triphenylformylmethylene – from arene cis-diols 145 phosphorane 629 – selective design of 145 Hunsdiecker reaction 51, 260, 261, 859 Hg(OAc)2 oxidation huperzine A 574, 596 – of amine to imminium ion 796 huperzine S 574 hirsutene 213, 249, 362, 363, 381, 418 Hurst–Whitham rearrangement 511 – isolation from Coriolus consors 361 hydrazine oxidation – synthesis via protoilludyl cation 384 – electrochemical 387 – total synthesis, Curran 389 hydrazone formation – total synthesis, Hudlicky 382 – a,b-unsaturated 735 – total synthesis, Little 386 1,4-hydride shift 237 – total synthesis, Mehta 386 – in acorane ring systems 236 – total synthesis, Tatsuta 381 hydrindanones – total synthesis, Wender 389 – energy differences 179 hirsutic acid 362, 363 hydroalumination reduction – isolation from Sternum hirsutum 361 – in juvenile hormone synthesis 218 Hofmann degradation, elimination 48, 534, hydroazulenes 213, 277 535, 739, 745, 791 – bibliography 333 – in ibogamine synthesis 792 – structures of 277 – of aspidospermine 32 hydroboration 53, 168, 287 – of codeine 27 – of alkene 811 – of codeine methiodide 29 – with 9-BBN 810 – of heroin methiodide 27 hydroboration–oxidation 368, 453, 482, 509, – of oxycodeine 28 585, 586, 785, 786 holosynthon (S,S)-(–)-hydrobenzoin ketal – definition of 134 – in resolution of ketones 745 Subject index 975 hydrogenation imine alkylation – catalytic 111 – asymmetric 774 hydrogenolysis imine hydrolysis – of benzylic hydroxyl 304 –ofZ-toE-enal 857 – of N–O bond 622 impact factor 1,5-hydrogen shift 373 – concept of 924 hydrojulilidine ring system 574, 592 incipient transformations 147 – stereochemical assignment of 576 – in enantiodivergent design 154, 147 – synthesis of 576 – of arene cis-diols 147 hydroquinone increase in intricacy 156 – oxidation to quinone 487 indigo 42 hydroxybarbatusol 486 – commercial synthesis 41 4-hydroxycephalotaxine 656 – synthesis 61 11-hydroxycephalotaxine 655, 656 indinavir 13, 43, 45, 95, 99, 909, 911, 921, 922 4-hydroxycrotonate – disconnection analysis 911 – [3+2] dipolar cycloaddition of 620 – HIV-I protease inhibitor 910 hydroxyfuran oxidation 294 – Merck synthesis of 909 hydroxyfuran–pyranulose rearrangement – treatment of HIV-1 909 – in bulnesene synthesis 294 indole-2-acetic acid b-hydroxy ketones – mechanism of decarboxylation 797, 798 – directed reduction of 442 indole-3-acetic acids a-hydroxylation – mechanism of decarboxylation 797, 798 – of ketones with molybdenum peroxide indole alkaloids 759 (MoOPH) 482 – bibliography 826 4-hydroxyphenylacetaldehyde 730 – biogenesis of 762 hypnophilin 386 – biological activities 761 – biosynthesis of 759, 761 i – general methods of synthesis for 531, Iboga alkaloids 763, 797 795 – biosynthesis of 788 – stereochemical relationships of 759 – from Vinca rosea 788 indolizidine alkaloids 847 – relationship to vinblastine and vincristine ingenane 789 – occurence in Euphorbiaceae and – structure elucidation 788 Thymalaeaceae families 469 ibogaine 789 – skeleton ring system 470 – from Tabernathe iboga 788 ingenol 213, 470, 478, 847 ibogamine 530, 531, 760, 789, 792, 793, 795, – bibliography 494 798, 800, 921 – biological activities 469 – bibliography 826 – disconnection analysis 471 – disconnection analysis 790 – esters of 469 – formal synthesis of, via coronaridine – in signal transduction and activation of 797 protein kinase C 470 – isolation 788 – isolation 469 – total synthesis, Bchi 790 – total synthesis, Winkler 475 – total synthesis, Kutney 794 inoloazepine – total synthesis, White 798 – intermediate in vindoline synthesis 776 ideal synthesis 97, 155 inositol – definition of 82 – from arene cis-diols 118, 145 imidate synthesis 695 – selective design of 145 976 Subject index inositol stereoisomers isoprenyl group – number of 145 – as aldehyde equivalent 299 – synthesis of 145 isoprenyl pyrophosphate 759 interconversion – in biosynthesis of indole alkaloids 762 –ofAspidosperma and Vinca/Eburnea isoquinuclidine skeletons 764, 786 –inIboga alkaloids 789 intramolecular acylation – by Diels–Alder cycloaddition 790, 791 – of N-acetyl enolate anion 866 isoretronecanol 529, 531, 617, 618, 625, 627, intramolecular [4+1] cyclopentene annulation 630, 631, 635 404 – bibliography 643 intramolecular olefination 863 – disconnection analysis 628 intramolecular [4+1] pyrroline annulation 636 – second-generation synthesis of 625 Intricacy Quotient (IQ) – total synthesis, Danishefsky 628 – definition of 129 – total synthesis, Hudlicky 628 inversion of configuration 172 – total synthesis, Leonard 627 iodolactonization 693, 694, 696, 699 – total synthesis, Muchowski and Ireland–Claisen rearrangement 389, 391, 700 Nelson 634 – in pancratistatin synthesis 699 – total synthesis, Pinnick 633, 634 isocephalotaxinone 656, 662 – total synthesis, Stevens 634 isocomene 42, 44, 213, 362, 363378, 403 isostrychnine 801, 807 – disconnection analysis 364 – isolation from Berkeya radula 361 j – isolation from Isocoma wrightii 361 Jacobsen epoxidation 912, 913 – synthesis of all four isomers of 378 – in indinavir synthesis 913 – total synthesis, Chatterjee 367 jasmone 362 – total synthesis, Hudlicky 374, 377 Jones oxidation 238, 259, 306, 370, 376, 432, – total synthesis, Oppolzer 363 546, 556, 609 – total synthesis, Paquette 367 juvenile hormone 213, 217 – total synthesis, Pirrung 370 – absolute configuration 217 – total synthesis, Wender 372 – bibliography 224 b-isocomene 366, 378 – disconnection analysis 219 – total synthesis, Hudlicky 377 – isolation 217 isocomenic acid 625 – (JH I), synthesis of 218 – relationship with zizanoic acid 412 – Platysamia cecropia (= Hyalophora – total synthesis, Hudlicky 374 cecropia L.) 217 isocyanate synthesis 707 – structure elucidation 217, 218 isoharringtonine 657 – total synthesis, Corey 218 L-isoleucine 619 – total synthesis, Edwards 218 isomeric mixtures – total synthesis, Johnson 223 – calculations of ratios 91, 93 – total synthesis, Kondo 219 – control of 95 – total synthesis, Masamune 219 – enrichment of 94 – total synthesis, Stotter 219 isomerization –ofZ-toE-enal 857 k isoperadione 486 Karenia brevis – isolation from Salvia bucharica 486 – taxonomic history 879 isoprene kaurane – Ni[COD]2-catalyzed dimerization of – skeleton ring system 449 207 Kazmaier–Claisen rearrangement 752 Subject index 977 kessane 213, 278, 280, 290 – from Karenia mikimotoi 878 – disconnection analysis 281 – from Protoceratium reticulatum 878 – synthesis of 286 lanosterol [2+2] ketene cycloaddition 395 – synthesis of 207 ketene–olefin cycloaddition latent transforms 150 – in retigeranic acid synthesis 394 – in synthetic design 154 keto amide synthesis latent symmetry 150, 152 – by intramolecular cyclization 866 – definition and examples of 150, 152 b-ketoesters laurenene 362 – decarboxylation 408 laurenyne 847, 848 – yeast-mediated reduction of 157, 638 Lawesson reagent 779 ketol rearrangement – thioamide formation with 780 – in quassin synthesis 485 lead potash glass a-keto oxime – use in pyrolysis 412 – oxidation to a-diazo-ketones 458 lead tetraacetate – synthesis from lactone 458 – for oxidative cleavage of enamide 666 3-keto phosphonate Lemieux–Johnson oxidation 738 – in palytoxin synthesis 901 lepadiformine 6 ketophosphonate synthesis – structure revision 5 – in palytoxin synthesis 895, 900 L-leucine khusanes – in biosynthesis of cephalotaxine esters 657 – isolation from vetiver oils 255 Leuckart–Wallach reaction 48 khusimol 256 LHASA program 130 – formal syntheses of 256 limonene 209, 419 khusimone 256, 262, 266, 318 – as chiral starting materials in total – asymmetric synthesis of 266 syntheses 271 – dissconnection analysis 257 – hydrogenation over Adam’s catalyst 406 – formal total synthesis of 270 (S)-(–)-limonene – isolation 255 – in retigeranic acid synthesis 394 – synthesis 267 Lindlar hydrogenation 379, 807 – total synthesis, Liu 262 – of acetylene 807 – total synthesis, Oppolzer 262 – of acetylene to cis-alkene 632, 806 kifunensine 155, 847, 848 linear polycyclic ethers 873 kinetic enolate anions 168 linear synthesis 98 kinetic methylation of 1,2-dione 662 a-lithioacetic acid Kitahara enone–ketal 453 – addition to aldehyde 859 – in aphidicolin synthesis 451 lithium tetramethylpiperidide 623 Knoevenagel reaction 48 – oxirane opening with 451 Kornblum oxidation 736, 738 longifolene 846, 847 longithorone A 872 l – biosynthetic pathway 873 lactone cleavage – total synthesis, Shair 873 – with BBr3 783 lovastatin 432 lactonization Luche reduction 182, 389, 391, 441, 477, 555, – Yamaguchi mixed anhydride method 869 556, 711, 713, 739, 740, 799, 800, 902 Ladder toxins 873 lycodine 574, 596 – biological activity 877 lycodoline 574 – from Gambierdiscus toxicus 875 lycopodine 43, 45, 108, 195, 530, 574, 804, 845, – from Karenia brevis 874 909, 922, 924 978 Subject index

– bibliography 599 – biological activity 877 – disconnection analysis 577 – from sturgeonfish 877 – isolation from Lycopodium complanatum – isolation from dinoflagellate 573 Gambierdiscus toxicus 876 – order of bond formation, in Heathcock’s – structure elucidation 876, 877 synthesis 584 – toxicity of 891 – total synthesis, Ayer 594 malonic ester synthesis 48 – total synthesis, Grieco 594 Mander’s reagent 475 – total synthesis, Heathcock 580 Mannich cyclization – total synthesis, Kraus 585 Mannich reaction 51, 534, 583, 585, 771 – total synthesis, Padwa 594 – in aspidospermidine synthesis 776 – total synthesis, Stork 577 – in daphnilactone synthesis 606 – total synthesis, Wenkert 593 – in gramine synthesis 805 Lycopodium alkaloids 573 – in spiroindolenine synthesis 805 – biological activities 574 – intramolecular 583, 609, 788 – biosynthesis of 573, 575 – of 2-veratrylindole 804 – general method of synthesis 591 marine polycyclic ethers – structure elucidation 573 – bibliography 881 lycoricidine 155, 200, 690, 696, 702, 709, 713, marine toxins 715, 719 – from epiphytic dinoflagellates 873 – cytotoxic activities of 689 – human poisoning from 873 – synthetic strategies 714 maritimol 449, 450 – total synthesis, Hudlicky 714 Matteson reagent 900, 901 – total synthesis, Ohta 714 – in palytoxin synthesis 895, 900 – total synthesis, Padwa 714 maysenine 851 – total synthesis, Paulsen 714 maysine 851 lycorine 529, 689, 690 – synthesis of 859, 863 – isolation from Narcissus maytansine 846, 851, 858 pseudonarcissus L. 689 – bibliography 879 Lycoris radiate 689 – biological activity of 851, 853 lysergic acid 529, 760, 802, 807 – biological profiles 847 – diethyl amide (LSD) 759 – convergent assembly of 856 – synthesis of 759 – disconnection analysis 852 – formal synthesis of 867 m – isolation from Actinosynnema pretiosum macleanine 574 851 macrocycles – isolation from Maytenus ovatus 851 – structures 871 – structure determination of 851 – synthesis of 850, 851, 858 – total synthesis, Corey 853 macrocyclization – total synthesis, Meyers 859 –ofN-acetyl enolate anion 866 maytansine esters – summary of methods 865 – structure elucidation of 851 macrolactonization maytansinol 851 – of esters of 2-pyridinethiol 859 – bibliography 879 – Yamaguchi method 859 – synthesis of 859, 863, 867 magic methyl reagent 319 McMurry coupling 509, 514 Magnusson ring contraction 382, 385 – in compactin synthesis 443 – mechanism of 413 Meerwein–Ponndorf–Verley reduction 51, 545, maitotoxin 876, 877 546 Subject index 979

Meerwein reagent 661, 709, 710 (–)-O-methylpallidinine 357 Meinwald–Cava ring contraction 1-methylpyrrolizidine 627 – in aphidicolin synthesis 456 (–)-methyl retigeranate 399 menthene mevalonic acid 759 – ozonolysis of 406 – in biosynthesis of indole alkaloids 762 meroquinene 537 mevinolin 432 – syntheses of 539 Michael reaction 48, 322, 461, 462, 560, 577, Merrifield 578, 586, 588, 629, 669, 765, 766 – solid-phase peptide synthesis 56 – base-catalyzed 588 mescaline 527, 529 – diastereoselective 476 meso compounds – enantioselective 462 – enzymatic desymmetrization of 117 – in aspidospermidine synthesis 776 metalation – in ibogamine synthesis 792 – of aryl bromide 859 – in strychnine synthesis 804 – of imine with methylmagnesium iodide – in vindoline synthesis 776 773 – of 2-pentanone with acrylonitrile 767 metallo-ene reaction 262, 265 – tandem, in compactin – transition states of, in khusimone synthesis 440, 441 synthesis 266 – transannular 664 metal-mediated [6+4] cycloaddition 479 microbial reduction meta photocyclization 390 – asymmetric 434 meta-photocycloaddition 241, 323, 373, 400 – with Aureobasidium pullulans – in sesquiterpene design 114, 116 NRRLY-12610 432 – in synthesis of rudmollin 321 milbemycins 845, 847, 848 – strategy in triquinane design 363 mitomycins 846, 847 methods of synthesis Mitsunobu reaction 53, 56, 394, 395, 439, 540, – class-oriented 191 639, 705, 707, 711, 713, 739, 740 – task-oriented 191 – with azide 745, 774 p-methoxy- or p-hydroxybenzoic acids – with diphenylphosphoryl azide 539 – Birch reduction of 853 modhephene 362, 363 O-methylation – synthesis 267 –ofa-diketone 662 Moffatt oxidation 318, 319, 595, 659, 660 – of phenol 535 molecular refractivity N-methylation 737, 743 – in structure determination 229, 246 methylenecyclopropane molybdenum-hexacarbonyl – [3+2] annulation 669 – for N–O bond reduction 712 – cycloaddition with cyclopentadiene 267 monensin 846, 847 – diene [3+2] annulation 268 monoterpenes a-methylene lactone synthesis 316 – as chiral starting materials in total – Danishefsky protocol 348 syntheses 271 – Grieco protocol 299, 345 morphine 41, 43, 133, 528, 530, 531, 627, 728, (+)-methyl homodaphniphyllate 730, 739, 741, 745, 804, 845, 921 – total synthesis of 606 – adjustment of stereochemistry at C-14 N-methylmaysenine 439, 853, 856, 857, 858, 733, 736 863, 865 – attachment of ethylaminobridge 29 – synthesis of 859 – bibliography 753 O-methylnorbelladine 689 – biomimetic approaches to 731 methyloxazaborolidine – biosynthesis in human cells 747 – in asymmetric reductions 666 – biosynthesis of 727, 730 980 Subject index

– C-14 hydroxylated derivatives 728 – total synthesis, Rigby 705 – congeners 728 Narciclassus poeticus L. 689 – degradation to phenanthrene 27 narcotine 528 – derivatives of 727 narwedine 689, 690 – disconnection analysis 732 Nazarov-type cyclization 51, 662 – dissonant relationships in 732 – vinylogous connectivity of 798 – enantiodivergent approach to 741 necine family – from codeine, by demethylation 26, 736 – source of pyrrolizidine alkaloids 617 – history 727 Nef reaction 48, 364, 367, 369 – isolation history (Serturner’s account) nelfinavir 911 727, 747 – HIV-I protease inhibitor 910 – methylation of 26 neopine 728 – structure elucidation 23, 26, 729 neopinone 728, 730 – total synthesis, Evans 736 neoquassin 479 – total synthesis, Gates 733 – structure elucidation of 480 – total synthesis, Mulzer 746 Nerine bowdenii 691 – total synthesis, Ogasawara 746 nerolidol 207 – total synthesis, Overman 741 network analysis 129 – total synthesis, Parker 739 nickel–p-allyl complex – total synthesis, Rice 736 – in confertin synthesis 318 – total synthesis, Taber 746 nicotine 529 – total synthesis, White 746 nitroalkene cycloadditions – Xray structure 30 – asymmetric 639 morphol – tandem [4+2]–[3+2] 639 – product of morphine degradation 27 o-nitrobenzenesulfonylhydrazide – synthesis of 27 – for reductive transposition of allylic Mukaiyama oxidation 864, 865 alcohols 488 – of primary alcohol 863 nitrone addition multi-component reactions – in compactin synthesis 443 – definition of 101, 121 2-nitrophenyl selenocyanate 243 a-nitrosoketone n – fragmentation to oxime-ester 535 Nakamura–Kuwajima aldol–pinacol sequence N-nitrosolactams 290, 292 – fragmentation reaction of 539 nalmetene 728 N–O bond reduction naloxone 727, 728 – with samarium iodide 710 naltrexone 727, 728 7-norbornyl cation 354 nanotechnology 930 S-norcoclaurine 727, 730 – relation to organic synthesis 922 norethindrone 208 – trends in 18 norfluorocurarine naproxen – in strychnine biosynthesis 802 – production of 111 norgestrel 208 narciclasine 529, 531, 690, 691, 709, 713, 716, norizaene 719 – total synthesis, Hoffmann 267 – cytotoxic activities of 689 normaysine 851 – disconnection analysis 706 noroxymorphone 728 – mechanism of action 689 nucleophilic aromatic substitution – total synthesis, Hudlicky 709 – photostimulated 658 – total synthesis, Keck 709 nucleoside FR-900848 847 Subject index 981 o – factors influencing the practice of 923 ochratoxin 112 – future evolution trends 931 – synthesis of 112, 113 – guide to the literature 953 a-ocimene 487 – impact of new technology on 927, 928 b-ocimene 487 – influence by industry, government 931 trans-a-ocimene – mentoring practices in 925, 926 – as diene components, perovskone – outlook and future perspectives 917 synthesis 488 – transference of skills 926 trans-b-ocimene – trends in funding of 925 – as diene components, peroskone synthesis ortho-ester formation 488 – synthesis from ester 348 Ohira–Bestmann acetylene synthesis 245 ortho-metalation olefin–acetylene cyclization – history of 121 – formic acid-catalyzed 314 ortho-quinone synthesis 734 olefinations 53 overall yield olefin cleavage – calculations of, for multistep synthesis 92 – with osmium tetroxide/sodium periodate – definition of 97 451 Overman rearrangement 696 olefin–epoxide cyclization 7-oxabicyclo[2.2.1]heptane – trans annular 368 – intramolecular fragmentation, in compactin olefin isomerization synthesis 439 – rhodium promoted 385 7-oxabicyclo[2.2.1]heptene 443 olefin metathesis 57, 696 oxa-di-p-methane rearrangement 391 – discovery of 121 oxaspirocyclopentane annulation 451, 452 – in triquinane design 363 oxazaborolidine complex olefin synthesis – in asymmetric reductions 440 – by oxetane fragmentation 439 – in asymmetric reduction of enone 739, – by selenoxide elimination 345 741, 742 – by xanthate pyrolysis 440, 441 oxazine reduction ophiobolanes – with aluminum amalgam 711 – synthesis of 207 – with Mo(CO)6 712 opium – with tris(trimethylsilyl)silane 712 – historical milestones 729 oxetane synthesis 439, 512 – illicit use of 727, 747 oxidation 287, 854 – medicinal use 727 – of aldehyde to acid 697 opium alkaloids – of amine to amide 811 – history 727 – of arene C–H bonds 112 – historical milestones 727, 729 – of ketones to enones, with IBX 353 Oppenauer oxidation 51, 457, 582, 583 – of primary alcohol with O2/Pt, selective – Woodward modification of 735 307 oranocerium addition – of unactivated C–H bonds 112 – to ketones 295 oxidation of arenes, by toluene dioxygenase Orchidaceae families of plants 118, 137, 639 – source of pyrrolizidine alkaloids 617 oxidation of indole organic synthesis – to 3-chloroindolenine 796 – competition for resources 930 oxidative cleavage – diversity of reserach options 929 – of enone to ester-aldehyde 547 – diversity of work force 929 – of tertiary alcohols with Pb(OAc)4 291 – factor affecting future development 920 – diols 298 982 Subject index oxidative deprotection – isolation from the soft coral Palythoa – of PMB group 695, 708 toxica 891 oxidative homologation – mechanism of action 904 – of alkyl halide 290 – possible steroisomers of 891 oxidative radical cyclization – strategic order of connectivity 895 – in estafiatin synthesis 302, 303 – structure elucidation 891, 892 oxidopyrylium–olefin cycloaddition – total synthesis, Kishi 892 – intramolecular 472 palytoxin carboxylic acid 902 oxidoreductase enzymes – conversion to palytoxin 895, 896 – in synthesis 117 – deprotection 901 oxirane synthesis – structure of 892 – with sulfonium ylide 742 pancratistatin 529, 531, 690, 702, 845 oxonium salt – cytotoxic activities of 689 – condensation of, with tryptamine in – derivatives of 690 eburnamonine synthesis 788 – disconnection analysis 693 oxonium ylide – etymology of 715 – [3+2] dipolar cycloaddition of 780 – first asymmetric synthesis of 108, 120 – from diazoesters 595 – minimum pharmacophore 690, 692 oxyallyl species – synthesis from pinitol 702 – generation from 1,1,3-trichloroacetone – synthetic strategies 703 475 – total synthesis, Danishefsky 696 oxycodone 728 – total synthesis, Haseltine 703 a-oxygenation 512 – total synthesis, Hudlicky 197, 696 oxymercuration 168, 289, 438, 855 – total synthesis, Kim 699 – intramolecular, in dehydrokessane – total synthesis, Li 703 synthesis 290 – total synthesis, Magnus 703 oxyselenation – total synthesis, Rigby 703 – of olefins 434 – total synthesis, Trost 703 ozone – unnatural derivatives of 692 – discovery of 48, 51 Pancratium littorale 689 ozonolysis 306, 343, 344, 345, 375, 462, 505, Pancratium maritimum 691 511, 556, 579, 580, 583, 631, 661 panepophenanthrin 847, 849 – in damsin synthesis 306 paradigm shift – of veratryl to muconate 805 – infuture developments of organic synthesis 920, 922 p passifloricin A 5 palladium-catalyzed amination 666 – structure revision 4 – of allylic acetate 668 (–)-patchino 507, 518 palladium-catalyzed cyclization 666 a-patchoulene 35, 36, 38 palytoxin 43, 46, 90, 850, 873, 877, 901, 902, b-patchoulene 35, 36, 38, 502 903, 921 c-patchoulene 35 – bibliography 905 b-patchoulene oxide 502 – biological activity of 891 patchoulene oxide 502, 517 – convergent assembly of 893 b-patchoulene rearrangements – disconnection analysis 892 – in taxol synthesis 502 – Hawaiian mythology of 904 patchouli alcohol 291, 325, 328, 502, –inZoanthus species 891 516, 517 – isolation from ohter Palythoa – Bchi’s synthesis of 38, 794 species 891 – conversion to a-bulnesene 290 Subject index 983

– from rearrangement of a-patchoulene phenyl trimethylammonium tribromide oxide 37 – bromination and dehydrobromination – oxidative cleavage of, with lead reagent 318 tetraacetate 290 phlegmarine 574 – structure proof of 23, 35 phorbol 213, 470, 475, 845 patchouli alcohol acetate – bibliography 494 – pyrolysis of 36, 37 – biological activities 469 pattern recognition 134 – disconnection analysis 471 Paulsen–Danishefsky lactone 702, 713 – esters of 469 Pauson–Khand reaction 53, 56, 243, 245, 246, – first asymmetric total synthesis of 474 478 – in signal transduction and activation of pea seedling amine oxidase protein kinase C 470 – in trachelanthamidine synthesis 635 – isolation 469 Penicillin V 41, 43 – total synthesis, Cha 475 pentalenene 362, 363, 380, 403 – total synthesis, Wender 471 pentalenic acid 362, 363, 380, 403 phorbol esters peradione 486 – as tumor promoters 470 – isolation from Perovskia abrotanoides photochemical cyclization Kerel 486 – of enamide 705, 708 perhydroquinolone photochemical cycloaddition 262, 263, 290, – intermediate in aspidospermine synthesis 298, 371, 381, 383, 386, 388, 476 767 – in dehydrokessane synthesis 289 Perkin reaction 48 – in estafiatin synthesis 299 perovskone 213, 485, 486, 488, 909, 922 – intramolecular 371, 416 – bibliography 495 – in triguinane synthesis 363, 416 – disconnection analysis 486 photochemical rearrangement – isolation from Perovskia abrotanoides – of dienone283, 297 Kerel 485 – of verbenone to chrysanthenone 510, – synthesis by cascade cyclization 103, 511 489 photocyclization – total synthesis, Majetich 486, 490 – in narciclasine synthesis 705 perruthenate oxidation 508 photostimulated aromatic substitution 661 Peterson olefination 53, 56, 310, 311, 407, 408, phthalimide deprotection 631, 632 785 physostigmine 741 – in eburnamonine synthesis 786 picrotoxinin 846, 847 Petrzilka reaction 364 Pictet–Spengler reaction 50, 51, 543, 553, 554, PGE2a 727, 761, 765, 773, 781, 782, 785, 796, 797 – formal synthesis 16 – in eburnamonine synthesis 780, 786 PGF2 44 –inb-carboline synthesis 788 phenol – in vincamine synthesis 788 – nitrosatin of 734 – of indole into the iminium salt 794 p-phenolic alkylation – of tryptophane derivatives 195 – in cedrene synthesis 235 – stereoselectivity of acid-catalyzed vs. phenylalanine thermal conditions 783, 784 – in biosynthesis of cephalotaxine 657 pinacol rearrangement 258, 292, 663, 664 p-phenylphenylurethane –inb-bulnesene synthesis 290 – as directive group 100 – in zizaene synthesis 267 phenylselenation pinene – of olefins 391 – air oxidation to verbenone 510 984 Subject index

– as chiral starting material in total – Lewis acid catalyzed 321 syntheses 271 – of norbornadiene 307 – in taxol synthesis 510 proenantiotopic differentiation pinitol 149 – principles of 146 – enantiodivergent design 150 proenantiotopic functionality 149 – in pancratistatin synthesis 702 proenantiotopic plane – structural relationship to pancratistatin – in enantiodivergent design 350 151, 696 proenantiotopic plane of symmetry 639 piperine 528 progesterone 42, 44, 208 piperonal 709 – synthesis of 114, 209 b-pipitzol 246 D-proline platynecine 617, 618, 636, 637, 638 – in asymmetric synthesis of cephalotaxine – total synthesis, Hudlicky 635 670 – total synthesis, West 640, 641 prostaglandin enones polarity adjustments 186 – stereoselective reduction of 100 Polonovski reaction 51 prostaglandins 42, 845 polyene cyclization prostaglandin PGF2a 846, 847 – in aphidicolin synthesis 455 protecting groups polymerase chain reaction 59 – design function of 99 polypeptide framework – directing effects of 100 – in vancomycin 873 – management of, in palytoxin synthesis polyquinanes 361 896, 901 Pomeranz–Fritsch isoquinoline synthesis 534, – use in synthesis 99, 190 535 proteomics pravastatin 432 – relation to organic synthesis 922 preakuammicine 761 protoceratin II – in biosynthesis of indole alkaloids 762, – from Protoceratium reticulatum 877, 878 802 pseudo-Aspidosperma alkaloids 761 precedent – synthesis of 797 – analysis of 139 pseudoguaianes 280, 304 prenyl bromide – historical milestones 304 – as equivalent of a-bromo acetaldehyde pseudoguaianolides 304 510 pseudosymmetry 151 prenyl group pseudovincadifformine 795 – as latent carboxylic acid equivalent 309, Ptychodiscus brevis 343 – taxonomic history 879 – oxidative cleavage of 343 pulegone 419 prestrychnine 802 (R)-(+)-pulegone – in strychnine biosynthesis 802 – in retigeranic acid synthesis 394 preswinholide A fragment – as chiral starting materials in total – in Nicolaou’s synthesis 870 syntheses 271 – in Paterson’s synthesis 870 Pummerer rearrangement 51, 53, 195, 670 prezizaene 256 putrescine 619 prezizanol 256 pyrazine carboxylic acid primary alcohols – asymmetric hydrogenation of 912 – selective oxidation of 306 pyridinium salts Prins reaction 369 – additions of nucleophiles to 560 – intramolecular 322 – 1,2-reduction of 791 – in zizaene synthesis 259, 261 pyrogallol 696 Subject index 985 pyrroline [4+1] annulation 622, 641 – structure elucidation 531, 532 – in supinidine synthesis 624 – synthesis 7, 41 – via azide-diene cycloaddition 141 – total synthesis, Stork 539 pyrroline rearrangement – total synthesis, Woodward 534 – in strychnine synthesis 810 quinolone synthesis 578, 767 pyrrolizidine alkaloids 151, 158 – mechanistic options 813 – australine family 617 quinotoxine 532, 537, 921 – biological activities 617 – conversion to quinine 533, 534 – biosynthesis of 618, 619 – N-bromination 534 – enantiodivergent synthesis of 638 – synthesis of 534 – general method of synthesis for 639 quinuclidine synthesis 540 – hyacinthacine family 617 – isolation from Asteraceae family 617 r – necine family 617 radical addition 400 – representative members of 617, 618 – to acetylene 438 – synthetic strategies 634, 640 radical cascades 113, 710, 740 pyrylium generation – in synthesis of Amaryllidaceae – from hydroxypyranones 472 constituents 267 – of aziridinyl imine 702 q – in cedrene synthesis 230, 243 quassin 213, 479 – in morphine synthesis 739 – bibliography 494 – in steroid synthesis 209, 212 – biological activities 479 – in zizaene synthesis 267 – disconnection analysis 480 – of aziridinyl imines 270 – isolation from the wood of Quassia amara – photochemical 710 479 radical cyclizations 113, 710, 740 – structure elucidation of 479 – endo cyclizations 671 – total synthesis, Grieco 480 – 5-exo-7-endo 302 – total synthesis, Valenta 483 – mechanism of 244, 269, 710 quaternary ammonium salts – in 7-deoxypancratistatin synthesis 702 – reductive cleavage of 773 – in synthesis of (–)-estafiatin and quaternary salt of b-carboline derivatives (+)-cladantholide 303 – reductive or alkylative – intramolecular of bromo acetal 560 cleavage of 796 – in triquinane design 363 quebrachamine 760, 761, 764, 770, 772, 773, – of Stork’s bromoacetal 303 794, 795 – tin-mediated 303 – comparison of Stork’s and Ban’s radical dehalogenation 697 intermediates 768 Ramberg–Bcklund reaction 51 – oxidation of, to chloroindolenine 797 ramoplanin 873 – total synthesis, Kutney 775 Raney nickel 639 quinidine 532 – discovery of 51 quinine 41, 43, 528, 529, 531, 532, 537, 802, 804, Raney nickel reduction 534 921, 924 Rauwolfia alkaloids 541 – bibliography 566 reaction environment – conversion of quinotoxine 537 – control of 172 – disconnection analysis 533 reaction mass efficiency (RME) – formal syntheses 532 – definition of 97 – isolation of 531 reaction space 129, 149 – Roche synthesis of 538 – definition of 82 986 Subject index reaction yield regiochemistry – definition of 97 – control in enzymatic reactions 169 – reporting of 120 – of enolate formation 169 reagent space 147 regiocontrol rearrangements – issues of 167, 168 – of allylic carbinol 806 Reimer–Tiemann reaction 780 – of intermediates in Bchi’s ibogamine – abnormal 782 synthesis 793, 794 – in eburnamonine synthesis 780 reduction relay synthesis – catalytic 110 – of aphidicolin 453 – of amide to aldehyde 697 reproducible reactions – of aryl halide 735 – discussion of 191 – of enone, asymmetric 667 reproductibility – of 1,4-enones 297 – of published results 923 – of enones, with dissolved metal 452 reserpine 41, 43, 529, 531, 542, 557, 560, 760, – of indolyl ketone 771 802, 807, 915, 921, 922 – of nitrile to aldehyde 308 – bibliography 566 – of the N–O bond with samarium iodide 709 – biological activities 541 – of benzamide to aldehyde 698 – biosynthesis of 541 reductive amination 51, 630, 639, 663, 664, 741, – disconnection analysis 544 742 – isolation from Tonduzia longifolia 541 reductive coupling – isolation from Rauwolfia 759 –ofa-diketone with nitrile 734 – isolation from Rauwolfia sepentina 541 reductive cyclization – structure elucidation 541 – of nitro esters with copper chromite 629 – synthesis 41 reductive detosylation 739, 740 – total synthesis, Hanessian 558 reductive formylation 452 – total synthesis, Martin 552 reductive SRN1 reaction 661 – total synthesis, Mehta 555 redundant operations or reactions – total synthesis, Shea 558 – definition of 107, 109 – total synthesis, Stork 558 – in aspidospermidine synthesis, Heathcock – total synthesis, Wender 558 775, 819 – total synthesis, Woodward 544 – in daphnilactone synthesis, Heathcock 775 resolution 735 – in isocomene synthesis, Wender 107 – of acids via diastereomeric amides 438 – in lycopodine synthesis, Heathcock 109, – with camphor sulfonic acid 547, 551 259, 576, 580, 606, 775 – with D-tartaric acid 536 – in pancratistatin synthesis, Hudlicky – with (+)-malic acid 788 109 – with L-tartaric acid 913 – in zizaene synthesis 259 – wit quinidine 806 reflexivity 129, 151 R-reticuline 727, 730 Reformatsky reaction 48, 306, 319, 376, 403, S-reticuline 727, 730 606, 624, 671, 673 retigeranic acid 42, 44, 213, 362, 363, 404, 419, – intramolecular 608 420, 845 – kinetic 374 – convergent synthesis of 105 –ofc-bromocrotonate 231, 622 – design connectivity 197 – regioselective 404 – disconnection analysis 393 – vinylogous 374, 375 – isolation and structure determination 392 Reformatsky reagent – isolation from Himalayan lichens Lobaria – from ethyl bromoacetate 305 retigera 361 Subject index 987

– isomers of 392 ritonavir – structure determination 363 – HIV-I protease inhibitor 910, 911 – synthesis of 207 Ritter reaction 912 – total synthesis, Corey 394 – in indinavir synthesis 913 – total synthesis, Hudlicky 403 Robinson annulation 171, 221, 256, 258, 365, – total synthesis, Paquette 394 366, 502, 503, 774 – total synthesis, Wender 399 – in quassin synthesis 481 retro-aldol reaction – Yoshikoshi modification 367 – acid-catalyzed 352 (–)-rosmarinecine – of bicyclo[3.2.1] system 352 – total synthesis, Denmark 639, 640 retro-Claisen reaction 353 rudmollin 278, 321 – of bicyclo[3.2.1] system 351, 353 retro-ene reaction s – of BOC group 698 salutaridine synthase retro-Mannich reaction 772 – in morphine biosynthesis 728 – in indole alkaloid synthesis 779 salutaridinol 730 – of dehydroaspidospermidine 767 salvadione – of dehydroaspidospermine 767 – total synthesis 488, 490 retronecine 617, 618, 619, 637, 638 Samarium iodide reduction – total synthesis, Hudlicky 635 –ofa-hydroxyketone 505 retrorsine 617, 618 – of thiophenyl group, tosylate, N–O bond 709 retrosynthetic analysis sample content – by SYNGEN program 132 – determination 120 retrosynthetic resonance santonin 304, 325 – definition of 141 – photochemical dienone rearrangements ring contraction 173, 174, 176, 282, 396 of 281 – by Chan rearrangement 504 – photochemical rearrangement of 296, 297 – by Favorskii rearrangement 174 saquinivir 911 – in aphidicolin synthesis 458 – HIV-I protease inhibitor 910 – in bulnesol synthesis 285 sarcodictyin 849 – of diazoketone 459 sarpagine 541, 542 – thallium(III)-mediated 240 sarracine 618 – Wolff rearrangement 174 Schlosser modification 53 ring expansion 176, 287, 383 Schmidt rearrangement 51, 537, 765 – in aphidicolin synthesis 458 – intramolecular, in aspidospermidine – in dehydrokessane synthesis 289 synthesis 773, 774 – in khusimone synthesis 262 scientific misconduct – in retigeranic acid synthesis 394 – discussion of 197, 930 – Johnson–Semmelhack steroid synthesis SciFinder search 200 262 scopaduicic acid A and B 741 – of a [3.2.0] system 292 secodaphniphylline 603, 604 – oxidative 475 – biosynthetic intermediate 606 – oxidative, furan-pyranone 472 secologanin 759 – via pinacol rearrangement 258 – in biosynthesis of indole alkaloids 762 – via thio–pinacol rearrangement 396 selective deprotonation – with ethyl diazoacetate 280 – of thiopyran 222 ring junction stereochemistry 177 L-selectride ring size – for reduction of ketones to axial alcohols – modifications 173 460 988 Subject index selenoxide spiro-annulation – in olefin synthesis 297, 708 – Kuwajima’s aldol-pinacol method 665 – sigmatropic rearrangement of 243 spiroazanonane 662 selenoxide elimination squalene – in enone synthesis 344, 434 –inDaphniphyllum alkaloid biogenesis –ina,b-unsaturated carbonyl synthesis 297 605 a-selenylation – synthesis of 207 – of ketones 343 Staudinger reaction 539, 540 seniciphyllic acid 619 stemarane sequential [4+2] and [3+2] cyclizations – skeleton ring system 449 – in vindoline synthesis 780 stemmadenine 761 L-serine – in biosynthesis of indole alkaloids 762 – in taxol synthesis 514 stemodane sesquiterpene lactones 278, 341, 845 – skeleton ring system 449 seychellene stemodane diterpenes – synthesis 113 – structure 449 Shapiro reaction 433, 435, 508 stemodin 449 Sharpless epoxidation 56, 58 step economy 98 1,5-sigmatropic hydrogen shift stereochemistry –incis-methylvinylcyclopropanes 309 – of alkylation of decalinones 169, 170 [2,3]-sigmatropic rearrangement 591 – control of, in enzymatic reactions 169 – of allylic sulfoxide to allyl sulfenate 440 stereochemistry adjustment – of selenoxide 432 – by oxidation/reduction 857 sigmatropic rearrangements stereocontrol – in hydroazulene synthesis 280 – issues of 167, 169, silphinene 362, 363, 380 stereoselectivity silphiperfol-6-ene – definition of 169 – synthesis 113 stereospecificity Simmons–Smith reaction 236, 237, 260, 261, – definition of 169 316, 317 steroid synthesis 208 –ofN-acetyl-3-ethyl-2-piperideine 773 – by enyne cyclotrimerization 114 skeletal rearrangements – by intramolecular cyclizations 115 – in hydroazulene synthesis 280 Stetter reaction 110, 189, 405 Skraup quinoline synthesis 48 Stevens rearrangement 50, 51, 641 SN2 substitution on nitrogen 536 Stieglitz rearrangement sodium benzoate –ofN-chloroamine 595 – aqueous, for mild hydrolysis 709 Stiles reagent 314 solid-state and combinatorial synthesis 59 Stille coupling 53, 700, 705, 713 solvolytic rearrangement 287 Still rearrangement 397, 399 – in bulnesol synthesis 286 Stobbe condensation 48 – in hydroazulene synthesis 280, 286 Stork alkylation 260 – in terpenoid synthesis 288 Stork enamine reaction 56 songorine Stork–Eschenmoser hypothesis – model studies 259 – of enzymatic squalene cyclization 208 – synthesis of 257 structure assignments Sonogashira coupling 700, 709, 710 – compilation of incorrectly assigned – in pancratistatin synthesis 699 compounds 850 (–)-specionin – of intermediates in Bchi’s ibogamine – synthesis of 141 synthesis 794 Subject index 989 structure elucidation – of alkylborane 811 – by degradation, Woodward’s perspective swainsonine 847, 848 812 Swern oxidation 269, 300, 301, 441, 442, 504, – milestones in 23 539, 540, 608, 663, 664, 740, 896, 898 strychnine 41, 43, 528, 530, 531, 760, 800, 801, – in palytoxin synthesis 895, 897, 899, 900 802, 803, 812, 845, 921, 924 Swinholide A – bibliography 826 – antifungal and cytotoxic acitivities 869 – biosynthesis of 802 – synthesis, Nicolaou 870 – disconnection analysis 803 – synthesis of 869 – isolation from Strychnos ignatii 800 symmetry analysis – isolation from Strychnos nux vomica 800 – of bicyclo[3.2.1]octenone building blocks – mechanistic details in Woodward’s 350 synthesis of 808 symmetry issues – oxidative degradation 807 – in synthetic design 146 – structure elucidation 801 symmetry space 147, 150 – total synthesis, Bodwell 810 – definition of 136 – total synthesis, Rawal 809 syn-1,3-diols – total synthesis, Woodward 804 – stereoselective generation of 344 strychninolone SYNGEN program 130, 131 – intermediates in strychnine degradation SYNLIB 807 – CAD program 131 Strychnos alkaloids 801 synthesis – biological activity of 801 – definition 3 – biosynthesis of 802 – discussion of principles and issues 87 – isolation 801 – economy 98 – structures 801 – history 3 Strychnos ignatii – history of accomplishment 3, 921 – isolation from 800 – mission of 3, 15 Strychnos nux vomica – problem analysis, flowchart 88 – isolation from 800 – purpose of 3 Strychnos skeletons 763 – relative energy index 98 sulfoxide–sulfenate rearrangement 439 – step number limit of 92 supinidine 531, 617, 618, 625, 626, 627 – tools and components of 4 – air oxidation of 619 – trends in 8 – bibliography 643 – unsolved problems 10, 11 – disconnection analysis 621 synthetic methods – optical rotation data 620 – SciFinder search of titles for 198 – purification 641 synthetic operation – second-generation synthesis of 625 – relative index of difficulty 98 – total synthesis, Hassner 626 synthetometrics 129 – total synthesis, Hudlicky 621 synthon – total synthesis, Kametani 626 – definition of 186 – total synthesis, Macdonald 620 system resonance 142 – total synthesis, Robins 626 – definition of 141, 406 – total synthesis, Sarkar 626 – total synthesis, Tufariello 620 t Suzuki coupling 53, 711, 712, 753, 902 tabersonine 761, 763 – in palytoxin synthesis 895, 900, 901 tactics Suzuki–Miyaura cross-coupling 712, 799, 810 – definition of 165 990 Subject index tandem – for oxidation of alcohols to aldehydes 786 – definition of 121 thalidomide 51 – radical cyclizations 389, 391 thebaine 530, 728, 730 – reactions 101 – symmetry-based design 160 tandem and multi-component reactions 60 thermal [2+2] cycloreversion 388 tandem 5-exo-dig cyclization 295 thermodynamic control 168 target relevant complexity 135 – of enolate anions 168 taxane diterpenes 499 thexyl borane – biosynthesis of 500 – hydroboration with 451 taxane skeleton thioacetal hydrolysis – synthesis of 36 – in palytoxin synthesis 899 taxinine 499, 500 thioamide synthesis 633 taxol 12, 13, 18, 19, 90, 213, 362, 514, 515, 845, thio-ketal desulfurization 256 847, 921, 924 thioketal hydrolysis 866 (+)-taxol 507 thioketal synthesis 771 (–)-taxol 507 – from vinylogous amides 814 – bibliography 520 thioimino ester synthesis 633 – biological activities 500 thio–pinacol rearrangement 396 – biosynthesis 500 thiopyran – chronology of syntheses 207 – in juvenile hormone synthesis 219 – disconnection analysis 501 L-threonine 619 – fragmentation-based approach 135 Thymalaeaceae families 469 – from Taxus brevifolia 499, 516 Tiffeneau–Demjanov ring expansion 238 – isolation and structure of 499 tigliane – semisynthesis from baccatin III 500 – occurence in Euphorbiaceae and – side-chain attachment 505 Thymalaeaceae families 469 – symmetry-based design 153 – skeleton ring system 470 – synthesis of 207 toluene dioxygenase 59 – total synthesis, Danishefsky 513 – in aromatic dioxygenation 118, 709 – total synthesis, Holton 502 topographical relationship – total synthesis, Kuwajima 513 – definition of 143 – total synthesis, Mukaiyama 513 topological analysis 87, 130, 143 – total synthesis, Nicolaou 507 topological relationships – total synthesis, Wender 510 – definition of 143 Taxol 44, 499 – in angular–linear triquinanes 144 taxusin 499, 500 – in hexose–inositol design 144 – bibliography 520 tosylate reduction – synthesis of 502, 513 – with samarium iodide 710 Taylor–McKillop ring contraction tosyliminium salt – in cedrene synthesis 242 – cyclization of 804 tazettine 741 trachelanthamidine 531, 617, 618, 625, 626, tedanocolide C 849 627, 630, 632, 635 tedanolide C 850 – bibliography 643 teicoplanin 873 – biomimetric synthesis from terpene synthesis 205, 767 homospermidine 635 a-terpineol 42, 209, 921 – disconnection analysis 628 – synthesis of 42, 207 – second-generation synthesis of 625 tetracycline 847 – total synthesis, Danishefsky 628 tetrapropylammonium perruthenate – total synthesis, Hudlicky 625 Subject index 991

– total synthesis, Leonard 627 – condensation of, with secologanin 802 – total synthesis, Pinnick 633, 634 – condensation with aldehydes 770 – total synthesis, Robins 634 – in biosynthesis of indole alkaloids 762 transannular cyclization strategy tryptophan – in indole alkaloid synthesis 798 – in biosynthesis of indole alkaloids 762 trans-decaline synthesis tryptophyl bromide 551, 765, 783 – from enones by dissolved metal reduction – alkylations of 560, 770 463 tubelactomicin 849 trans-diaxial opening turneforcidine 617, 636, 637, 638 – of epoxides 698 – total synthesis, Hudlicky 635 trans-halo ether – total synthesis, West 640, 641 – reductive cleavage of 294 (–)-turneforcidine 618 transition-metal-catalyzed cross-coupling Turner–Wilson ring contraction 382 reactions 58 two-directional synthesis 151 transition states L-tyrosine 727, 730 – Cram 172 tyrosine – Felkin–Ahn 172 – in biosynthesis of cephalotaxine 657 1,2-transposition – of carbonyl group 171 u 1,3-transposition ubiquitin 847 – of allylic alcohols 315 Ugi multicomponent condensation 56 transposition uleine 760 – of heterocycles to carbocycles 176 umpoled synthons 186 trichloroethyl carbamate umpolung reagents 110, 186, 187 – reductive deprotection of 579 unsaturated aldehyde synthesis 854, 856, 857 tricyclovetivanes a,b-unsaturated aldehyde synthesis 856 – isolation from vetiver oils 255 urea 42 (+)-trihydroxyheliotridane 638 – synthesis 50 (–)-trihydroxyheliotridane 638, 639 trihydroxyheliotridanes 149 v – enantiodivergent design of 151 vacuum pyrolysis 784 trimethylsilylcyanide vancomycin 847, 872 – for cyanohydrin synthesis 239 – total synthesis of 873 b-trimethylsilylethyl carbamate vanillin 488 – fluoride-assisted hydrolysis of 786 veatchine 530, 531 b-trimethylsilylethyl protecting group 861 veratrine 528 2-trimethylsilylmethyl-3-acetoxypropene verbenone 510 – reagent for [3+2] annulation 669 vernolepin 18, 42, 44, 90, 213, 341, 351, 745, 921 triquinanes 213, 361 – bibliography 357 – bibliography 420 – disconnection analysis 342 – radical cascade design of 114 – isolation from Vernonia hymenolepis 341 – stereochemical analysis by NMR 377 – Ogasawara’s intermediate for 349 – structure determination 361 – topographical similarities with – synthesis of 374, 403 hydroazuolene lactones 314 tropinone 42 – total synthesis, Danishefsky 346 tropone – total synthesis, Grieco 343 – 1,8 addition of Grignard reagent 299, 300 – total synthesis, Ogasawara 349 – 1,8-Grignard addition 300 vernomenin tryptamine 765 – isolation from Vernonia hymenolepis 341 992 Subject index

– topographical similarities with – rearrangement of, to pyrrolines with hydroazuolene lactones 314 TMSI 810 vetivanes – synthesis of 624 – biogenetic relationship to zizaenes vinylboronic acid 255 – in playtoxin synthesis 900, 901 vetiver oil vinylcyclopropane–cyclopentene rearrange- – composition of 255 ment 56, 59, 102, 139, 141, 249, 375, 379, – from Vetiveria zizanioides 255 385, 404, 408 a-vetivone 270 – discovery of 634 b-vetivone 255, 270 – degenerate version of, in isocomene Vilsmeier reaction 285, 472, 474 synthesis 372 – in bulnesol synthesis 284 – in aphidicolin synthesis 451 Vilsmeier-type formylation 663 – in specionin synthesis 625 vinblastine 45, 530, 760, 773, 780, 789 – in triguinane synthesis 363, 374, 375, – biological activities 761 621 – in extracts of Catharanthus roseus 788 – low temperature version 625 – synthesis of 43 – in retigeranic acid synthesis 400 Vinca skeletons 763, 764 – photochemical (degenerate) 373 vincadifformine 760, 764, 770, 772, 773, 776, – rhodium-mediated 384 778, 780 – thermal by FVP 384 – bibliography 826 vinylcyclopropanes – total synthesis, Wenkert 772 – pyrolysis of 407 – total synthesis, Kuehne 772, 778 – synthesis of 452 vincadine 795, 797 vinyl ether synthesis vincamine 760, 761, 786, 788 – from allylic alcohol 454 – bibliography 826 vinylogous acid chloride – synthetic strategies for 787 – reduction with zinc–copper couple 580 – total synthesis, Oppolzer 787 vinylogous amide synthesis 633 vincoside 759, 761 vinylogous Reformatsky reaction – in biosynthesis of indole alkaloids 762 – in cedrene synthesis 234 vincristine 773, 780, 789 – in pyrrolizidine alkaloid design 624 – biological activities 761 – in triquinane design 375 – in extracts of Catharanthus roseus 788 vinylogous urea synthesis 902 vindoline 760, 764, 773, 776, 780, 789 – in palytoxin synthesis 895 – bibliography 826 vinylsilane cyclization – cycloaddition approaches to 779 – in compactin synthesis 443 – overview of strategies for 777 vinyl stannane – total synthesis, Boger 779 – in pancratistatin synthesis 699 – total synthesis, Bchi 777 Vitamin B12 41, 44 – total synthesis, Kuehne 777 Vitamin B12 807 – total synthesis, Kutney 777 Vitamin D 349 vinylaziridine–pyrroline rearrangement 623, vittatine 689, 691 624, 635 von Braun degradation – in pyrrolizidine alkaloid synthesis 635 – of aspidospermine 32 – lithium iodide mediated 625 vulnerability 129 – trimethylsilyliodide mediated 625 Vycor columns vinylaziridines – conditioning with PbCO3 for pyrolysis – additions of nucelophiles to 698 384, 412 – cuprate addition to 693, 697 – in flash vacuum pyrolysis 376, 404 Subject index 993

Vycor glass y – for flash vacuum pyrolysis, PbCO3-treated Yamada reagent 697 384 yeast-mediated reduction – of keto esters 639 w yessotoxin Wagner–Meerwein rearrangement – from Protoceratium reticulatum 877, 878 – in bulnesol synthesis 282 yield – solvolysis 285 – current definitions 97 Wagner–Meerwein shift 36, 284, 287, 292 yield calculations Weinreb amide 472 – for multistep synthesis 91 Weinreb–Dolby enamine 658, 659 yield optimization 93 Wender [5+2] cycloaddition 56 yohimbane Wenkert–Bohlmann bands 35 – alkaloids synthesis 195 Wharton olefination 313 yohimbine 541, 542, 559, 761 Wharton reduction 311, 312 17-yohimbone 357 Wharton transposition 314 yuzurimine 603, 604 whole cell fermentation W-vincadifformine 780 – of aromatic compounds 696 – total synthesis, Kuehne 778 Wichterle reaction 325 Wieland–Gumlich aldehyde 802 z – in strychnine biosynthesis 802 zaluzanin C 278, 295 Wieland–Mischler ketone 288, 451 zampanolide 871 – R-(–)-enantiomer of 483 – synthesis of 869 – in bulnesol synthesis 284 zaragozic acid 847 Wilkinson catalyst 50, 281, 283 zaragozic acid C 848 – decarbonylation of aldehyde 387, 705 zinc–acetic acid reduction Wittig reaction 53, 56, 258, 261, 293, 298, 386, – in ibogamine synthesis 792 347, 388, 394, 402, 440, 456, 513, 539, 540, zinc–copper couple 556, 631, 635, 699, 896, 899 – in vinylogous Reformatsky – Conia–Dauben-modification of 89, reaction 622 256 zinc-mediated reduction – in palytoxin synthesis 897, 899 – of acetoxy ketones 549 – with diethyl [(thiophenyl)methyl]- – of bromo lactones 549 phosphonate 739 –ofb-halo ethers 549 Wittig reaction (Horner–Emmons zizaene 213, 255, 256, 262, 267 modification) 406, 901 – bibliography 272 – in palytoxin synthesis 895 – dissconnection analysis 257 Wittig rearrangement 51 – formal syntheses of 256 Wolff–Kishner reduction 240, 241, 290, 369, – isolation from vetiver oils 255 370, 397, 451, 453, 486, 487, 733, 734, 791 – structure 255 – in ibogamine synthesis 792 – total synthesis, Kim 267 – Kabalka modification 394, 396 – total synthesis, Wiesner 257 Wolff rearrangement 51, 366, 458 zizaene (khusane) sesquiterpenes 256 – in ring contractions 366 zizanoic acid 213, 255, 256 – dissconnection analysis 257 x – formal syntheses of 256 xanthate synthesis 244 – from khusimone 264 – from alcohols 441 – structure of 255 xestocyclamine 849, 850 – synthesis from khusimone 262