List of Synthons

Appendix I: List of Synthons

Hanspeter Pfander

This Table lists the main synthons used in the synthesis of carotenoids. The numbers refer to the pages on which details of the preparation or the use of these synthons are reported. For additional synthons the reader is referred also to the Tables in Chapter 2 Parts I and II.

C2-Compounds acetylene dimagnesium dibromide BrMg = MgBr 166. 167

0 diethylcyanomethyl-phosphonate II 244 (EtO)2P'.../ eN

0 ethyl diethylphosphonoacetate II 140,146,148,173,176. (EtO)2P '.../ COOEt 177. 182, 244, 246, 249

0 methyl diethylphosphonoacctatc II 121 (EtO)2P '.../ COOMe

vinyl ethyl ether -7'o~ 29 vinyl magnesium bromide -7'MgBr 121,147,167,168 vinyl magnesium chloride -7'MgCI 183,187,188,248 vinyl methyl ether -7'0/ 29 332 H. Pfandcr

C3-Compounds

acrolein O~ 146, 148

0 l-carbethoxyethylidene 277 /"0 A.yPPh3 triphenylphosphorane

l-methoxy-I-methylethene 29 Isopropenyl methyl ether Jo/

propenyl ethyl ether ~O~ 29

HOOC~ L-serine o OH 322 NH,

C4-Compounds

OH 0 (R)-3-hydroxybutyric acid 154 ~OH

Cs-Compounds

4-acetoxy-2-rnethylbut-2-enal ACO~O 123

2-methylbuta-I,3-dienyl ethyl ether ~O~ 29

3-methylbuta-I,3-dienyl ethyl ether ~O~ 29

[3-(5,5-dimethyl-I,3-dioxan-2-yl)- 277 but-2-enyll triphenyl-phosphonium e e O~ chloride CJPh3P~ " 0

(3-ethoxycarbonyl)but-2-en-l-yl 0 O~ 279 diethylphosphonate (EtO),P II~" .... 0 Appendix I: List of Synthons 333

2-hydroxy-2-methylbut-3-enoic 127 acid ethyl ester ~COOEI OH

5-hydroxy-4-methyl-2(5H)- 128 furanone HO~O

3-methylbut-2-ene-I,4-dial-l- 277 acetal; 3-(5,5-dimethyl-I,3-dioxan- 2-yl)-2-methylpropenal o~J:}

2-methylbut-2-ene-I,4-dial-l- 277 acetal; 3-(5,5-dimethyl-1 ,3-dioxan- 2-y\)-but-2-enal o~:}

3-methylbut-2-en-l-ol 147,319 ~OH

3-methyl-l-trimethylsiloxybuta- 31 1,3-diene; silyl enol ether ~OSi(Me)3 0 methyl diethyl 3-methyl-4- 137, 142, 153 phosphonobut-2-enoate (EIO)2P"~ "COOMe

C6-Compounds

3-methylpent-l-en-4-yn-3-o1 214 ~ 3-methylpcnt-2-en-4-yn-l-ol 122,202,263 ~OH 334 H. Pfander

Cs-Compounds

oct-4-ene-2,7 -dione; 133, 163, 186, 192

Cs-diketone

140,142 6-methylhept-5-en-2-one ~O

(4R,6R)-4-hydroxy-2,2,6-trimethyl• 211 cyclohexanone Xv HO;j",~ 6-oxoisophorone ote 4,169,184,281,282 isophorone 169

CIO-Compounds

tetramethyl 1,8-diphosphono-2,7- 206 II ~"P OMe (MeO) O~P ':?' II ( )2 dimethylocta-2,6-dien-4-yne; 2" 0 acetylenic ClQ"bis-ylide

~-cyc1ocitral 273,60,91,305

OH 2,7-dimethylocta-1,7-dien-4-yne- 116 3,6-diol

oOH Appendix 1: List of Synthons 335

2,7 -dimethy locta-2,4,6-trien-8- 241 alnitrile

2,7 -dimethylocta-2,4,6-triene-1 ,8- 8, ,II, 66, 89, 92, 96, dial; 116ff, 136,152, I 67ff, 181ff, 189, CIO-dialdehyde 195,198,203,215, 241ff, 246, 253, 275, 284,286,301

2,7-dimethylocta-2A,6-triene-I,8- 11,173,176,177 BrPh pee di-(triphenyl phosphonium) 8e~ 3 """ PPh3Br dibromide; Cwdiphosphonium salt

gerany I acetate 197,316 ~OAC geranyl chloride ~CI 313

4-hydroxy-2,3,6- 193 trimethylbenzaldehyde HoM+0

H-(2R)-lavandulol ~OH 91

Iinalool 134,144

~OH

3,3-dimethyl-6-(2-ethyl-I,3- 35 dioxolan-2-yl)-hex-2-one

o 0 L.J 336 H. Pfander

2,3,4-trimethylbenzaldehyde ira 193

2,3,6-trimethy1benzaldehyde 192 '6c: a (+ )-camphor ;£ 3,190 0 (-)-a-pinene pr 194,523

C 13-Compounds

(3S,5R,6R)-6,7-didehydro-3,4- 204 dihydro-a-ionone-3,5-diol; 'grasshopper ketone'

(5£)-6,1 O-dimethy lundeca-5,9- 246 dien-2-one; geranylacetone ~o a-ionone 3, 173, 183, 186, 325 ~a

~-ionone 57, 162,167,181, 248,262,249,272, ~a 273,303 Appendix I: List of Synthons 337

y-ionone 189 ~o

'I'-ionone 132,137,261,271 ~o

C I5"Compounds ethynyl-~-ionol 57, 303 ~ (all-E)-farnesol 150,249,317 ~OH farnesyl bromide 136,137 ~Br tram-nerolidol ~ 136 OH vinyl-~-ionol 311 ~I OH

CwCompounds

6-[2' ,6' ,6'-trimethyl-cyclohex -\ '-en• 264 yIJ-4-methyl-hexa-2,4-dien-l-al ~o 338 H. Pfander

Cl9"Compounds

8-[2',6'.6'-trimethyl-cyclohex-1 '-en• 265 yI1-2,6-dimethyl-octa-2,4,6-trien-l• al ~o

crocetindialdehyde 12,89,91, 134, 140, o " 142, 143, 146, 147, 153, ISS, 156, 158, 191,192 geranylgeranyl bromide ~Br 141 trans-geran y IIi nalool 139

Appendix II: List of Naturally Occurring Carotenoids Prepared by Total Synthesis

Marc Lanz and Hanspeter Pfander

In the Key to Carotenoids [1), where 563 naturally occurring carotenoids are listed, literature references for the total synthesis of 148 carotenoids are given. Since 1986, 54 new carotenoids have been isolated from natural sources [2) and some of these have been synthesized. In the following 'Appendix' new syntheses of carotenoids published since 1986 are listed. Included are new syntheses of carotenoids already listed in the Key to Carotenoids as well as syntheses of new carotenoids. According to the general policy of the Editors the reader is advised to use both the Key to Carotenoids and this 'Appendix' for complete information. The Key to Carotenoids includes some carotenoids which may not be natural products, such as the 5,8-epoxides which are generally considered to be artifacts but which are commonly found in natural extracts. Syntheses of such compounds are included in this 'Appendix'. The total synthesis of Z-isomers, however, is treated in Chapter 3.4. and therefore not included here.

7 CAS: 423-70-2 a-Carotene, (6'R)-p,E-Carotene

Synth., [3) 340 M. Lanz and H. Pfander

51 CAS: 39668-21-8

(2R)-~,~-Caroten-2-ol

HO " " " "

C4oHs6 O Synth" [4]

57 CAS: 106356-02-9 Isocryptoxanthin, (4R)-~, ~-Caroten-4-ol

" " " " - OH C4oHs6 O Synth" [5]

61 CAS: 106356-05-2 4-Hydroxy-a-carotene, (4R,6 'R)-~,£-Caroten-4-o1

Synth" [5]

113 CAS: 39668·26-3

(2R,2'R)-~,~-Carotene-2,2'-diol

HO OH

Synth" [4] Appendix II: Natural Carotenoids; Total Synthesis 341

118 CAS; 144-68-3 Diatoxanthin, (3R,3'R)-7 ,8-Didehydro-~, ~-carotene-3,3 '-diol OH

Synth., [6]

119 CAS: 144-68-3 Zeaxanthin, (3 R,3' R)-~, ~-Carotene- 3,3 '-di 0 I OH

Synth., [7,8,9]

197 CAS 28082-20-4 Crustaxanthin, (3S ,4S,3 'S,4'S)-~, ~-Carotene- 3,4,3' ,4' -tetrol OH OH

HO - OH Synth., [10,11] 342 M. Lanz and H. Pfandcr

198 CAS 29488-00-4 Heteroxanthin, (3R,5 R, 6R,3 'R)-7',8' -Didehydro-5 ,6-dihydro-p, p-carotene-3,5 ,6,3' -tetrol

Synth., [12]

202 CAS: 35804-89-8 Mimulaxanthin, (3S,5R,6R,3 'S ,5 'R ,6'R)-6, 7 ,6',7' -Tetradehydro-5 ,6,5' ,6' -tetrah ydro-p, p-carotene-3,5,3',5 '-tetro I

'" .-r " OH HO.cr

Synth., [13]

204 CAS: 98502-74-0 3,4,3',4 '-Tetrahydroxy -pirardixanthin, (3R,4S ,6R,3 'R,4'S,6 'R)- 5,6,5' ,6' -Tetrahydro-p, p-carotene-3,4,3',4' -tetrol OH : OH " " :Q ',\,"" -...... ;:: \",. , ex ", HO'" 0 OH

Synth., [14] Appendix II: Natural Carotenoids; Total Synthesis 343

212 CAS: 86105-69-3 Mactraxanthin, (3S ,5R,6R,3 'S,5'R,6'R)-5 ,6:5',6 '-Tetrahydro-p, p-carotene-3,5 ,6,3' ,5' ,6' -hexol

' " \\\'"""" ~OH HO ::. HO

Synth., [12]

234 CAS: 27780-09-2 Neoxanthin, (3S,5R,6R,3'S,5'R,6'S)-5',6'-Epoxy-6,7-didehydro-5,6,5',6'-tetrahydro-p,p-carotene-3,5,3'-triol "" .-:/ " OH £t" OH HO

Synth., [15]

250 CAS: 25548-02-1 Neochrome, (3S,5 R,6R,3' S,5 'R ,)-5' ,8' -Epox Y-6, 7 -didehydro-5 ,6,5',8' -tetrahydro-p, p-carotene-3,5,3' -triol

OH ,C("" .-:/ " OH HO

Synth., [15] 344 M. Lanz and H. Pfandcr

259 CAS: 126-29-4 Violaxanthin, (3S,SR,6S,3'S,S'R,6'S)-S,6:S',6'-Diepoxy-S,6,S',6'-tetrahydro-~,~-carotene-3,3'-diol

Synth., [9,16]

296 CAS: \06356-06-3 4' -H ydroxyechinenone, (4'R)-4' -Hydroxy -~, ~-caroten-4-one OH

Synth., [6]

341 CAS: 55906-76-8 Trikentriorhodin, (3S,SR)- 3,8-Dihydroxy-K,X -caroten-6-one

Synth., [17] Appendix TI: Natural Carotenoids; Total Synthesis 345

353 CAS: 50906-61-1 Mytiloxanthin, (3R,3'S,5'R)-3,3' ,8' -Trihydroxy-7 ,8-didehydro-~, K -caroten-6-one

"o =

Synth., [18]

369 CAS: 3351-86-8 Fucoxanthin, (3S,5S,6R,3'S,5'R,6'R)-5,6-Epoxy-3,3',5'-trihydroxy-6' ,T-didehydro-5,6,7,8,5',6'-hexahydro• ~, ~-caroten-8-one 3 '-acetate OCOCH3 HO"~ ~. "....'.

Synth., [19, 20]

406 CAS: 472-61-7 Astaxanthin, (3SJ'S)-3,3'-Dihydroxy-~,~-carotene-4,4'-dione o OH

HO o

Synth., [9] 346 M. Lanz and H. Pfander

439 CAS: 54783-71-0 C.p.450, (2R,2'R)-2,2'-Bis(4-hydroxy-3-methylbut-2-enyl)-~,~-carotene

Synth., [21]

440 CAS: 90139-11-0 C.p.473, (2R,2' S)-2' -(4-Hydroxy -3-methy Ibut -2-eny 1)-2-(3-methy Ibut -2-eny 1)-3' ,4'-didehydro-1 ',2 '• dihydro-~, 'I'-caroten-I '-01

Synth., [22]

441 (2R,6R,2'R,6'R) CAS: 11031-47-3 Sarcinaxanthin, (2R,2'R)-2,2'-Bis(4-hydroxy-3-methylbut-2-enyl)-y,y-carotene

Synth" [23,24] Appendix II: Natural Carotenoids: Total Synthesis 347

447 CAS: 28386-06-1 Decaprenoxanthin, (2R,6R,2' R,6'R)-2,2' -B is( 4-hydroxy -3-methy Ibut -2-eny 1)-E,E-carotene

(~"1 -II, lX'".'"", OH ...-:

Synth., [25]

452 CAS: 106927-21-3 Trisanhydrobacterioruberin, (2S)-2,2' -Bis(3-methylbut-2-enyl)-3,4,3' ,4'-tetradehydro-1 ,2-dihydro-'1', \jI-caroten-I-ol

Synth., [26]

455 CAS: 30403-58-8 Monoanhydrobacterioruberin, (2S,2'S)-2-(3-Hydroxy-3-methylbuty 1)-2'-(3-methy Ibut -2-enyl)-3,4,3' ,4'-tetradehydro-1 ,2, I ',2'• tetrahydro-\jI,\jI-carotene-l, I '-diol

OH ~ OH

Synth., [27] 348 M. Lanz and H. Pfander

456 CAS: 32719-43-0 Bacterioruberin, (2S,2'S)- 2,2'-Bis(3-hydroxy-3-methylbutyl)-3,4,3' ,4'-tetradehydro-l ,2, l' ,2'-tetrahydro-'lf, 'If- carotene-I, 1'-diol j OH

iOH

Synth., [28]

473 Sintaxanthin, 7' ,8'-Dihydro-7'-apo-~-caroten-8'-one

Synth., [29] 475 3-Hydroxy-sintaxanthin, (3R)-3-Hydroxy-7' ,8'-dihydro-7'-apo-~-caroten-8'-one

Synth., [29] Appendix II: Natural Carotenoids; Total Synthesis 349

478 OH-Sintaxanthin-5,6-epoxide, (3S,SR, 6S)-S,6-Epoxy-3-hydroxy -S,6, T ,8' -tetrahydro-T-apo-p-caroten-8 '-one

Synth., [9, 30]

484 CAS: 75715-17-2 (3S,SR,6S)-5,6-Epoxy-3-hydroxy-S,6-dihydro-8'-apo-p-caroten-8'-a!

CHO

Synth., [9, 30]

497 CAS: 120963-63-5 (3S,SR,6S)-S,6-Epoxy-S,6-dihydro-l O'-apo-p-carotene-3,1 O'-dio!

CH 20H

Synth., [9,30]

502 CAS 17237-68-2 Apo-lO'-vio!axanthinal, (3S,SR,6S)-S,6-Epoxy-3-hydroxy-S,6-dihydro-l O'-apo-p-caroten-l O'-a!

CHO

Synth., [9,30] 350 M. Lanz and H. Pfandcr

505 CAS: 80952-82-5 Persicaxanthin, (3S,5R,6S)-5,6-Epoxy-5,6-dihydro-12'-apo-p-carotene-3, 12'-diol

Synth., [9, 30)

506a CAS: 120021-88-7 Persicachrome, (3S,5R,8R)-5,8-Epoxy-5,8-dihydro-12'-apo-p-carotene-3, 12'-diol

Synth., [9,30)

506b CAS: 120053-62-5 Persicachrome, (3S,5R,8S)-5,8-Epoxy-5,8-dihydro-12'-apo-p-carotene-3, 12'-diol

CH20H

Synth., [9, 30)

509 CAS: 62777-81-5 Apo-12'-violaxanthinal, (3S,5R,6S)-5,6-Epoxy-3-hydroxy-5,6-dihydro-12'-apo-p-caroten-12'-al

CHO

Synth., [9, 30) Appendix II: Natural Carotenoids; Total Synthesis 351

552 CAS: 69020-32-2 Actinioerythrin, (3S,3'S)-3,3'-Dihydroxy-2,2'-dinor-~,p-carotene-4,4'-dione 3,3'-diacyJate

Acyl-O O-Acyl o C38H4804 Synth., [8] (as diol)

556 CAS: 54369-13-0 Pyrrhoxanthin, (3S,SR,6S,3'R)-S,6-Epoxy-3,3 '-dihydroxy-7' ,8'-didehydro-S,6-dihydro-1 0', II ',20'-trinor-p,p- caroten-19, II-olide 3'-acetate OCOCH3 o

Synth., [31,32,33]

558 CAS: 33281-81-1 Peridinin, (3S ,SR,6S,3 'S,5'R,6' R)-S, 6-Epoxy-3,3',S' -trihydroxy-6', 7' -didehydro-S ,6,5' ,6' -tetrahydro- 10',11' ,20'-trinor-~,p-caroten-19, II-olide 3'-acetate OCOCH3 o HO ~I" ~. ",,,

Synth., [19, 31, 32, 33, 34] 352 M. Lanz and H. Ffander

References fll O. Straub, Key to Carotenoids, 2nd Edition (ed. H. Pfander) Birkhauser, Basel (1987). [2] D. Kull and, H. Pfander, Carotenoids, Vol. fA (ed. G. Britton, S. Liaaen-Jensen and H. Pfander), p. 295 Birkhauser, Basel (1995). [3] K Bernhard and U. Hengartner, Abstr. 10th Int. Symp. on Carotenoids, Trondheim, CL2-1 (1993). [4] S. Gut, H. Wolleb and H. Pfander, He!v. Chim. Acta, 72, 496 (1989). [5J A. Haag and C. H. Eugster, Helv. Chim. Acta, 68,1897 (1985). [6] J. A. Haugan, S. Liaaen-Jensen, Acta Chem. Scand., 48, 899 (1994). [7J E. Widmer, M. Soukup, R. Zell, E. Bayer, H. P. Wagner and M. Imfeld, Helv. Chim. Acta, 73, 861 (1990). [8] M. Soukup, E. Widmer and T. Lukac, Helv. Chim. Acta, 73,868 (1990). 19J E. Widmer, M. Soukup and P. Spurr, Abstr. 9th Int. Symp. on Carotenoids, Kyoto, 5-5 (1990). [IOJ C. H. Eugster, in Carotenoids Chemistry and Biology, (ed. N. I. Krinsky, M. M. Mathews-Roth and R. F. Taylor), p. I, Plenum Press, New York, (1990). [I I] D. J. Buschor and C.H. Eugster, He!v. Chim. Acta, 73,1002 (1990). [12] c. H. Eugster, Pure Appl. Chem., 57, 639, (1985). ll3J A. Baumeler and C. H. Eugster, Helv. Chim. Acta, 74, 469 (1991). [14] U. Hengartner, Abstr. 9th Int. Symp. on Carotenoids, Kyoto, 5-4 (1990). [15] A. Baumeler, C.H. Eugster, He/v. Chim. Acta, 75, 773 (1992). [16J M. Acemoglu, P. Uebelhart, M. Rey and C. H. Eugster, He/v. Chim. Acta, 71, 9341 (1988). [17] A. KChopra, A.Khare, G. P. Moss and B. C. L. Weedon, J. Chem. Soc., Perkin Trans 1,1371 (1988). [18] A. KChopra, A.Khare, G. P. Moss and B. C. L. Weedon, J. Chem. Soc., Perkin Trans 1,1383 (1988). [19] Y. Yamano and M.lto, Chem. Pharm.Bull., 42, 410 (1994). [20] M.lto, Y. Yamano, S. Sumiya and A. Wada, Pure Appl. Chem., 66, 939 (1994). [21J H. Wolleb and H. Pfander, Hefv. Chim. Acta, 69, 646 (1986). [22] H. Wolleb and H. Pfander, He/v. Chim. Acta, 69, 1505 (1986). [23J J.P. Ferezou and M. Julia, Tetrahedron, 46, 475 (1989). [24] J.P. Ferezou, Meth. Enzymol., 213, 75 (1991). [25] M. Gerspacher and H. Pfander, Helv. Chim. Acta, 72, 151 (1989). [26J J-P. Wolf and H. Pfander, Helv. Chim. Acta, 69,62 (1986). [27] R. Muggli, R. Balmer and H. Pfander, Abstr. 10th Int. Symp. on Carotenoids, Trondheim, P2-3 (1993). [28] H. Pfander, in Carotenoids: Chemistry and Biology, (ed. N. I. Krinsky, M. M. Mathews-Roth, R. F.Taylor), p. 125, Plenum Press, New York, (1990). [291 J. A. Haugan, Acta Chem. Scand., 48, 657 (1994). [30] P. Uebclhart and C. H. Eugster, He!v. Chim. Acta, 71,1983 (1988). [31] M. Ito, Y. Hirata, Y. Shibata and K. Tsukida, 1. Chem. Soc., Perkin Trans 1, 197 (1990). [32J M. Ito, Pure Appl. Chem., 63,13 (1991). [33J M.Ho and Y. Yamano, J. Chem. Soc. Perkin Trans 1,1599 (1993). [34J M. Ito, Y. Yamano and Y. Shibata, Meth. Enzymol., 213,13 (1992). 353

List of Abbreviations

9-BBN 9-Borabicyclononane AcCI Acetyl chloride AD Asymmetric Dihydroxylation AD-mix-a Reagent for Sharpless Asymmetric Dihydroxylation: KJFe(CN)6, K2COJ, (DHQ)zPHAL (=Hydroquinidine 1,4- phtalazinediyl diether), K20s02(OH)4 [1500:1500:5:1] AD-mix-p Reagent for Sharpless Asymmetric Dihydroxylation: K,Fe(CN)6, K2COJ,(DHQD)z-PHAL (=Hydroquinine 1,4- phtalazinediyl diether), K,OsO,(OH)4 [1500:1500:5:1] BPCC Bipyridinium chlorchromate BTP Bridget tetrahydrophosphole BuLi Butyllithium CI2ZrCp2 Dichlorocyclopentadienyl zirconium DBN 1,5-Diazabicyclo[ 4.3.0]non-5-ene DBP Dibutyl phthalate DBU 1,8-Diazabicyc10[5 .4.0]undec-7 -ene DDQ 2,3-Dichloro-5,6-dicyano-I.4-benzoquione (+)-DET (+)-Diethyl tartrate DIBAH Diisobutylaluminium hydride (+)-DIPT (+)-Diisopropyl tartrate DMF N,N-Dimethylformamide DMF-DMA N,N-Dimethylformamide dimethyl acetal DMSO Dimethyl sulfoxide HMPA Hexamethylphosphoramide IPM Isopropenyl methyl ether LDA Lithium diisopropylamide LiAIH4 Lithium aluminium hydride MCPBA 3-Chlor-perbenzoic acid MEM 2-Methoxyethoxymethyl NaBH4 Sodium borohydride p-NBCI p-Nitrobenzoyl chloride NBS N-Bromosuccinimide Ni(acac), Nickel(Il) acatylacetonate NiCI,(dppp) Dichloro[ I ,2-bis(diphenylphosphino)propaneJnickel (II) PCC Pyridinium chlorchromate PhLi Phenyllithium PNB p-Nitrobenzoate PPh1 Triphenylphosphin PrLi Propyllithium SMEAH Sodium bis-(2-methoxyethoxy)aluminium hydride TBHP tert.-Butyl hydroperoxide TBS te rt. -B uty I-di methy 1- sil yl-cther TEMPO 2,2,6,6-Tetramethyl-I-piperidinyl-N-oxyl TES 2-([Tris{ hydroxy methyl ) methyl]amino )-I-ethane-sulfonic acid Tf,NPh N-Phenyltrifluoromethanesulphonimide THF Tetrahydrofuran THP Tetrahydropyran Ti(i-PrO)4 Titanium tetra-iso-propoxide TMEDA Tetramethylethylenediamine TMS Tetramethylsilane TMSOTf Trimethylsilyl triflate TPPO Triphenylphosphine oxide TsCI Toluolsulphonyl chloride TsOH Toluolsulphonic acid 355

Index

Ci.-Acetobromoglucose 293 Bacteriorhodopsin 234 Acetoxyaldehyde 123 Bacterioruberin 152ff Acetylene dimagnesium dibromide 163, 165, 170 Baker's yeast 4,149,167,170,282 Acety lenic carotenoids 201,220 Bastaxanthin 295 Acrolein 145,148 Betaine 85ff Actinioerythrol 198 BF,-etherate 27 lA-Addition 29,31 Bioavailability 288 AD-mix 318 Biphosphonium salt 94 Adonirubin 97 Birch reduction 24 Adonixanthin 97 Bisanhydrobacterioruberin 153, 155, 195 Aldol condensation 2,27,61, 123, 150, 168, Bixin 119,157 190ff, 213, 246, 261, 280 Butenolide 201. 208 Aleuriaxanthin 131,316 Alkenyllithium reagents 59 C.p,450 193,194 1-Alkoxydienes 29 C.p,473 193,195 Alkyllithium reagent see Grignard reagent Cw-alnitrile 241 Allenic carotenoids 201 C 1o-dialdehyde 8, II, 18,66,89,92,96, Alloxanthin 202,203,226,296,297 109,117, 119,120,134, Apo- and diapocarotenoids 121 136, 138, 144, 151, 167, 8'-Apo-~-caroten-8'-al 2,29,34,35,90,111, 168,171,181,182,189, 259,266,267,277,278 194, 198,202, 241ft, 8'-Apo-\jI-caroten-8'-al 90 253,274,278,284,301 12'-Apo-~-caroten-12'-al 96, 126, 187, 278, CIO-diphosphonium salt 173, 177, 178 see also C25 -apocarotenal CIO-diphosphonium II ~-Apo-12'-carotenal see C,,-apocarotenal C 14-aldehyde 263 8'-Apo-~-caroten-8'-oic acid 2,294 Cwaldehyde 264 ~-Apo-8'-carotenoic acid ethyl ester C 19-aldehyde 264, 266 see ethyl 8'-apo-~-caroten-8'-oate C2o-dialdehyde 152 8'-Apo-carotenoids 79 C,,-aldehyde 278,279,280 Apo-8'-~-carotcnoids 108 C25-apocarotenal 21,307

Apo- ~-carotenoids 276, 278 C30-aldehyde 90,280

Apo-2'-lycopenal 148 C45 -carotenoids 91

Apo-8'-lycopenal 145, 148, 149 C50-carotenoids 91,193,323 Arbusov conditions 117 C5-phosphonate 247 Arbusov reaction 88, 237ft, 243ff Cs-diketone 162 Arens-Van Dorp synthesis Cadiot -Chodkiewicz coupling reaction 70 Astaxanthin disulphate 300 Caloxanthin 297 Astaxanthin 2,8,11,79,92,93,110,165,173, (+)-Camphor 3,190 187,183,185,233,248,249,253, Cannizzaro reaction 34 259,269,283,284,296,297 Canthaxanthin 110 Astaxanthin, 13C-labelled 235 Canthaxanthin 34,79,172,182,259,267,269 Asymmetric dihydroxylation see Dihydroxylation Capsanthin 35, 190, 191 Asymmetric hydroboration 171 Capsorubin disulphate 300 Asymmetric synthesis 4,315 Capsoruhin 3,35,190,191,259,296,297,321 Aurochrome 177 I-Carbethoxyethylidene triphenylphosphorane 276 Azafrin 175,298 Ci.-Carotene see ~,E-carotene 356

~-Carotene see ~,~-carotene Dehydro-retro-carotene 166 ~,y-Carotene, 189 3,4-Dehydrorhodopin 141 ~-Carotene 136,221 Diatoxanthin 5,202,226 E-Carotene see c,E-carotene 7,8-Didehydroastaxanthin 117, 119 ~,~-Carotene 1,2,5,7,8, \3, 15, 18,29,58,66, 3,4-Didehydro-~,~-carotene 164 71,72,79,92,98,99,108,109, 5,6:5',6'-Diepoxy-5,6,5',6'- III, 117, 132, 162, 163,164, 182, tetrahydro-~,~-carotene 177,316 217,218,223,248,249,253,259, 1',2'-Dihydro-cjl,ljf-caroten-I'-01 297 261,263,264,265,267,269,274, I ',2'-Dihydro-cjl,ljf-caroten-1 '-01 sulphate 300 275,278,282,283,288,303,327,328 1,2-Dihydrolycopene 140,141 ~,~-Carotene, epoxidation 176 3,3'-Dihydroxyisorenieratene 193,297 ~,~-Carotene, l3C-Iabelled 235 Dihydroxylation 147, 318 ~,E-Carotene, 2, 186 Dihydroxylycopene 144 E,E-Carotene, 186, 187 ~-Diketone structure 201 y,y-Carotene, 189 Diketone 186,192 ~,~-Carotene-2,2'-diol, 167, 168 2,2'-Diketospirilloxanthin 150,151 ~,E-Carotene-3, 19-diol, 201 Dimerization 13 ~,~-Carotene-5,6:5',6'-diepoxide, 176 I, I '-Dimethoxy-I ,2, I' ,2'-tetrahydrolycopene 142 Carotenoid-protein complexes 234 [3-(5,5-Dimethyl-I,3-dioxan-2-yl)-but-2-enyll Carotenoids, labelled 233 triphenylphosphonium chloride 277 ~,~-Caroten-2-01 167 2,7-Dimethylocta-I,7-dien-4-yne-3,6-diol 116 Carotenoproteins 233 2,7-Dimethylocta-2,4,6 -triene Catalysed by iodine 217 -I,8-dialdehyde see CIO-diaIdehyde Circular Dichroism (CD) 205 2,7 -Dimethylocta-2,4,6-trien-8-alnitrile 241 Characterization of products 15 6,IO-Dimethylundeca-5,9-dien-2-one 246 Chiral pool 321 Diphosphonates 117 Chloroxanthin 144,145 Diphosphonium salts 117 Cis/trans nomenclature 217 Disulphonyl compounds 107 Citranaxanthin 2, 35, 259, 277, 278, 280 ~-Citraurin 191 ( EiZ)-isomerism 5, 8, 31, 62, 64, 80ff, 93ff, 106, Claisen condensation 214 125,136,202,205,217,252, Copper 70 270,274,280,285,286,289 Crocetin 157, 294 Echinenone 34 Crocetindialdehyde 12,34,89,91, III, 134, 136, Eno[ ether condensation 2, [70,264,266,267 140ff, 146, 147, I 53ff, 190ff,319 Eno[ ether 27 Crocin 294 1,2-Epoxy [ycopene 317 Crocoxanthin 202 [ ,2-Epoxy-~-carotene 148,316,317 Cross-coupling reaction 68 1',2'-Epoxy-y-carotene 90 u,Crustacyanin 233 I ,2-Epoxy-1 ,2-dihydro-~-carotene 149 Crustaxanthin 173, 174, 175 1,2-Epoxylycopene 90,148,149 Cryptocapsin 35, 190 Erythroxanthin 295 Cuprates 71 Eschscholtzxanthin 181 Cyanomethylphosphonate 243 3-Ethoxycarbonylbut-2-en-l-yl ~-Cyclocitral 60,91,271 diethylphosphonate 277 Cyclogeranyl sUlphone 112 Ethoxyethene 29 I-Ethoxyprop-I-ene 29 Darzens glycidic ester condensation 164 Ethyl 8'-apo-~-caroten-8'-oate 259,267,276,307 Decaprenoxanthin 195,196 Ethyl diethylphosphonoacetate [40, 142, 145,148 2'-Dehydroplectaniaxanthin 293 Ethynyl-~-ionol 57,303 357

Farnesol 149,249,317 5-Hydroxy-4-methyl-2(5H)-furanone 128 Farnesyl bromide 136 4-Hydroxy-2,3,6-trimethylbenzaldehyde 193 Formulation 287 4-Hydroxy-2,2,6-trimethylcyclohexanone 209 Fucoxanthin sulphate 300 Fucoxanthin 96,296,297,298 Iodine-catalysed isomerization 218 a-Ion one 3, 182,325 Geometrical isomers See (EtZ}-isomers ~-Ionone 57, 162,164,167,180,183, Geraniol 149 186, 189, 248, 249, 303, 304 Geranyl acetate 196,316 'I'-Ionone 132, 134,137,221, Geranyl bromide 134 261,262,263,271,272 Geranyl chloride 313 (-)-(S)-a-Ionone 172 Geranylacetone 246 (Z)-~-Ionylideneacetic acid 305 Geranylgeranyl bromide 138 ~-Ionylideneethanol 66 Glucosidation 294 Irradiation 106 Glycidic ester synthesis 263 2-lsopentenyl-3,4-didehydrorhodopin 156 Glycosides 293 Isophorone 169 Glycosy I esters 294 a-Isophorone 282 Grasshopper ketone 204 ~-Isophorone 282 Grignard coupling 263, 264, 267 Isoprene 125 Grignard reaction 2,55,80,116,121,137, Isorenieratene 71,192,225 147, 151, 153, 154, 162, Isozeaxanthin 166, 172, 173, 267, 298, 299 163, 168, 170, 182, 186, 192, 194, 198, 202, 248, 321 Grignard reagent 56,58,59,64, 71, Jones oxidation 108, 126 132, 187, 195 Julia olefination 8,109 Julia sulphone coupling 12 Heck reaction 66, 67 Heck -type coupling reactIOn 64, 66 Knoevenagel condensation 157 Hell-Vollhardt-Zelinsky reaction 237 Koenigs and Knorr 293 Heteroxanthin 176 Horner variation 219 Labelled, "C_ 235,236 Horner-Emmons condensation 145,148,158 Labelled, 14C_ 235 Horner-Emmons olefination 280 Labelled, 'H• 235 Horner-Emmons reaction Chapter 2 Part III.E., Lactucaxanthin 298, 299 2,21,25,62, 8~ 81,95, (-)-(2R)-Lavandulol 91 136,140,144,145,152, Lewis acid 27,29,30,31 173,174,175,176,179, Linalool 134,144 180,187,189,194.195, Lindlar catalyst 19, 109, 121, 134, 139, 237, 24 I. 244ff, 250, 251, 307 143,150, lSI, 157, 163, Horner-Wadsworth-Emmons reaction 165,170,171,174,179, see Horner-Emmons reaction, 192, 198,217,219,227,265 3-Hydroxy-12'-apo-~-caroten-12'-al 188 Lindlar hydrogenation 58 3- Hydroxybutyric acid 153 Loroxanthin 201 3-H ydroxy-~-cycloc itral 171. 190 L-serine 321 I '-Hydroxy-I ',2'-dihydrotorulene rhamnosIde 141 Lutein 4,6, 15, 2~ 21,98,187,188,195,298 Hydroxyechinenon 97 Lycopcnc 5,6,15,18,94, III, 128, 4-Hydroxy-~-ionone 175 132, 134, 136, 221, 236, 259 3-Hydroxyisorenieratene 193,297 Lycophyll 145 2-Hydroxy-2-methylbut-3-enoic acid ethyl ester 126 Lycoxanthin 145, 146,296,297 358

Mactraxanthin 176 Phosphonate 80,81,87,88,204 Mechanism 85 Phosphonium salt 80,81,83,92,96,203,270 Metal acetylide 55,56 Phosphorus ylide see Chapter 2 Part III.B., Methoxyethene 29 79,80,270 1-Methoxy-1-methylethene 29 Photooxidation 233 3-Methylbut-2-en-I-ol 147 Photoprotection 233 Methyl diethylphosphonoacetate 120 Photoreceptor 233 Methyl retinoate 106, 108 Photosynthesis 233 Methylbixin 131,157,158,230 Phytoene 136, 138,221 2-Methylbut-2-ene-I,4-dial 125 Phytofluene 136,138,139,221 2-Methylbut-2-ene-1,4-dial-I-acetal 277 (-)-a-Pinene 193, 323 3-Methylbut-2-ene-1,4-dial-1-acetal 277 Pinner reaction 127 3-Methy1but-2-enol 319 Plectaniaxanthin 90,321 6-Methylhept-5-en-2-one 140,142 Prenyl acetate \06 3-Methylpent-2-cn-4-yn-I-ol 121,202 Prolycopene 223 Michael addition 113 Propenyl ethyl ether 29 Michaelis reaction 88 Provitamin A activity 6 Michael-type addition 34 Pummerer reaction 108 Mimulaxanthin 204,205,227 Pyrrhoxanthin 201,208,209 Monoanhydrobacterioruberin 156 Montmorillonite 29 Reductive elimination 8 Mytiloxanthin 214, 226 Reformatsky reaction 55,62,80, 141, 142 Myxobactin 141 Reike magnesium 56 Myxol 90 Reinerapurpurin 201,193 Renieratene 192, 193, 225 Neoxanthin 180,227 Resolution of a racemate 2 Neurosporene 136,138 Retinal 5.16,31,98,99,223, Nickel catalyst 69 254,275,279 Norcarotenoids 198 Retinal, (all-£)- 328 Nostoxanthin 297 Retinoate 106 Retinoic acid \03 Okenone 193 Retinol 7 Ophioxanthin 295 Retinol, (all-£)- 328 Optical resolution 325 Retinyl acetate 314 Organometallic reaction see Chapter 2 Part II, Retro-carotenes 166 55,303 Retro-carotenoids 181 Orthoesters 30 Rhodopin 144,145 Oscillaxanthin 147,318,319 Rhodopin-20-al 201,218 Oscillol 147,318,319 Rhodopsin 234 Oxaphosphetanes 85, 86, 87 Rhodovibrin 142, 143,297 Oxidation state modification (OSM) 30 Rhodoxanthin 181 6-0xoisophoronc 4,9,170, 181ff, 282 Sarcinaxanthin 196,197 Palladium complex 106 SCOOPy 85 Palladium complex, 7t-allyl 64 Shapiro reaction 59,60,229 Palladium 64 Sharpless dihydroxylation 4 Peridinin sulphate 300 Sharpless epoxidation 149,168,175,179,315 Peridinin 5,201,208,209,212, Sharpless 147 213, 296, 297, 298 Sharpless-Katsuki epoxidation 4 359

Solubility 287 Vinyl magnesium chloride 182,186,188 Spheroidene 142, 144,234, 246ff, 253 Vinyl magnesium halides 59 Spheroidene, BC_ 235,251 Vinyl methyl ether 29 Spheroidenone 150,152 Vinyl-~-ionol 59,304,311 Spirilloxanthin 5, 142, 143,218 Vinylmagnesium bromide 147,120 Stereochemistry see Chapter 3 Part III.e. Vinyl magnesium chloride 272 Stereoselectivity 104 Violaxanthin 4,95,174,179,227,316 Steric hindrance 80 Vitamin A acetate 104,108,112,263,271,275 Sulphates 295 Vitamin A aldehyde 111 Sulphinates 103 Vitamin A 7, 13,57,61,62,79,103,106, Sulphone coupling see Chapter 2 Part IV., 107,121,164,166,181. 259, 136,311 261,263,264,269,270,272, Sulphone group 8 274,275,283 Sulphone method 182,208,209 Water-dispersible preparations 288, 289, 290 Sulphone 2,98,103 Whiting reaction 166 Swern oxidation 147,179 Williamson reaction 250 Symmetrical carotenoids 92 Wittig condensation see Wittig reaction Syn-anti isomerization 64 Wittig olefination see Wittig reaction Synthesis 'ex chiral pool' 3 Wittig reaction see Chapter 2 Part III, 2, 8, IOff, 16,22, 35, 62, Tetraacetoxypirardixanthin 15 66, 118ff, 125, 128, 134, 136, Tetraanhydrobacterioruberin 91 138ff, 145ff, 166ff, 185ff, 7,8,T,8'-Tetradehydroastaxanthin 93, 117 196ff, 203, 212, 214, 219, 3,4,3',4'-Tetradehydro-~,~-carotene 164, 165 243,251,261,269-286, 3,4,3',4'-Tetradehydro-~,~-carotene-2,2'-dione 180 307,319,327 3,4,3',4'-Tetradehydrolycopene 139, 140 Wittig-carbonylolefination see Wittig reaction 1,2.1',2'-Tetrahydrolycopene 140 Wittig-Horner reagents 204 1,2, I ',2'-Tetrahydrolycopene-I, I '-diol 297 3,4,3',4 '-Tetrahydroxy-pirardixanthin 24 X-ray analysis 18,22 Titanium 55 Titanium, low-valent 71,329 Zeaxanthin disulphate 300 Trans-geranyllinalool 138 Zeaxanthin 3,5,6, II, 12, 15,21,22,93, 110, Trans-Nerolidol 136 169,171,181,225,259,285,293, Triethylphosphonoacetate 244, 249 296,297 Trikentriorhodin 193,201,214 Zinc reagents 62 2,3,4-Trimethylbenzaldehyde 193 2,3,6-Trimethylbenzaldehyde 192 Trimethylcyclohexanone 9 Trimethylsilyl enol ether 30 Triphenylphosphine oxide 2,80,85,273 Triphenylphosphine 80,273 Trisanhydrobacterioruberin 12 Tunaxanthin 4

Unsymmetrical carotenoids 96

Vinyl ethyl ether 29 Vinyl magnesium bromide 167,194,195,248