Carotenoids Volume 2: Synthesis © 1996 Birkhiiuser Verlag Basel 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 ~OH Carotenoids Volume 2: Synthesis © 1996 Birkhauser Verlag Basel 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 OH 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 HO Synth., [6] 119 CAS: 144-68-3 Zeaxanthin, (3 R,3' R)-~, ~-Carotene- 3,3 '-di 0 I OH HO 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 OH 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 OH HO Synth., [9,16] 296 CAS: \06356-06-3 4' -H ydroxyechinenone, (4'R)-4' -Hydroxy -~, ~-caroten-4-one OH o Synth., [6] 341 CAS: 55906-76-8 Trikentriorhodin, (3S,SR)- 3,8-Dihydroxy-K,X -caroten-6-one OH 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 = HO 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"~ ~. "....'. 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.