e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

Total syntheses of epothilones A and B

D Meng, P Bertinato, A Balog, DS Su…

Index: Dongfang, Meng; Bertinato, Peter; Balog, Aaron; Su, Dai-Shi; Kamenecka, Ted; et al. Journal of the American Chemical Society, 1997 , vol. 119, # 42 p. 10073 - 10092

Full Text: HTML

Citation Number: 309

Abstract

Convergent, stereocontrolled total syntheses of the microtubule-stabilizing macrolides epothilones A (2) and B (3) have been achieved. Four distinct ring-forming strategies were pursued (see Scheme 1). Of these four, three were reduced to practice. In one approach, the action of a base on a substance possessing an acetate ester and a nonenolizable aldehyde brought about a remarkably effective macroaldolization see (89→ 90+ 91; 99→ 100+ 101) ...

N/A Structure

~%

EPOTHILONE C Structure

(2S,3S,4R,5R)-1-(benzyloxy)-6-(1,3-dithian-2-yl)-2,4,6-trimethyl-5-((triphenylsilyl)oxy)heptan-3-ol Structure

(2S,3S,4R,5R)-1...

~%

EPOTHILONE C Structure

(2R,3R,4R,5R)-3-((tert-butyldimethylsilyl)oxy)-6-(1,3-dithian-2-yl)-2,4,6-trimethyl-5-((triphenylsilyl)oxy)heptanal Structure

(2R,3R,4R,5R)-3...

~%

EPOTHILONE C Structure

(3R,4R,5S)-3-(2-(1,3-dithian-2-yl)propan-2-yl)-5-((S)-1-(benzyloxy)propan-2-yl)-4,7,7,8,8-pentamethyl-1,1,1-triphenyl-2,6-dioxa-1,7-disilanonane Structure

(3R,4R,5S)-3-(2...

~%

EPOTHILONE C Structure

(1E,3Z)-1-methoxy-2-methyl-3-[(trimethylsilyl)oxy]-penta-1,3-diene Structure

(1E,3Z)-1-metho...

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

(3S)-3-(methoxymethoxy)-6-(trimethylsilyl)hex-5-yn-2-ol Structure

(3S)-3-(methoxy...

~%

EPOTHILONE C Structure

(S)-2-(methoxymethoxy)-5-(trimethylsilyl)pent-4-ynal Structure

(S)-2-(methoxym...

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

(2S,3S,4R)-2-((S)-1-(benzyloxy)propan-2-yl)-3,5-dimethyl-3,4-dihydro-2H-pyran-4-ol Structure

(2S,3S,4R)-2-((...

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

(1S)-[(1E)-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethynyl]-3-butenyl acetate Structure

(1S)-[(1E)-meth...

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

(3R,4R,5S,6S)-6-((S)-1-(benzyloxy)propan-2-yl)-3-(iodomethyl)-2-methoxy-3,5-dimethyltetrahydro-2H-pyran-4-ol Structure

(3R,4R,5S,6S)-6...

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

4-Formyl-2-methylthiazole Structure

4-Formyl-2-meth...

~%

(3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)hexa-1,5-dien-3-ol Structure

(3S)-2-methyl-1...

(2S)-1-((tetrahydro-2H-pyran-2-yl)oxy)-5-(trimethylsilyl)pent-4-yn-2-ol Structure

(2S)-1-((tetrah...

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

(S,E)-2-methyl-1-(2-methylthiazol-4-yl)hexa-1,5-dien-3-yl (3R,5R,6R,7S,8S)-7-((tert-butyldimethylsilyl)oxy)-3-hydroxy-4,4,6,8-tetramethyl-5-((triphenylsilyl)oxy)tridec-12-enoate Structure

(S,E)-2-methyl-...

~%

EPOTHILONE C Structure

(S,E)-2-methyl-1-(2-methylthiazol-4-yl)hexa-1,5-dien-3-yl (3S,5R,6R,7S,8S)-7-((tert-butyldimethylsilyl)oxy)-3-hydroxy-4,4,6,8-tetramethyl-5-((triphenylsilyl)oxy)tridec-12-enoate Structure

(S,E)-2-methyl-...

~%

EPOTHILONE C Structure

(S,E)-2-methyl-1-(2-methylthiazol-4-yl)hexa-1,5-dien-3-yl (3S,5R,6R,7S,8S)-7-((tert-butyldimethylsilyl)oxy)-4,4,6,8-tetramethyl-3-((triethylsilyl)oxy)-5-((triphenylsilyl)oxy)tridec-12-enoate Structure

(S,E)-2-methyl-...

~%

EPOTHILONE C Structure

12,13-bismethylene-12,13-secoepothilone Structure

12,13-bismethyl...

~%

EPOTHILONE C Structure

N/A Structure

N/A Structure

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

(S,E)-4-(6-iodo-3-(methoxymethoxy)-2-methylhex-1-en-5-yn-1-yl)-2-methylthiazole Structure

(S,E)-4-(6-iodo...

~%

EPOTHILONE C Structure

(3R,4R,5S)-3-(1,1-dimethoxy-2-methylpropan-2-yl)-4,7,7,8,8-pentamethyl-5-((S)-pent-4-en-2-yl)-1,1,1-triphenyl-2,6-dioxa-1,7-disilanonane Structure

(3R,4R,5S)-3-(1...

~%

EPOTHILONE C Structure

(3R,4R,5S)-3-(2-(1,3-dithian-2-yl)propan-2-yl)-4,7,7,8,8-pentamethyl-5-((S)-pent-4-en-2-yl)-1,1,1-triphenyl-2,6-dioxa-1,7-disilanonane Structure

(3R,4R,5S)-3-(2...

~%

EPOTHILONE C Structure

(3S,4S,5R,6R)-4-((tert-butyldimethylsilyl)oxy)-7-(1,3-dithian-2-yl)-3,5,7-trimethyl-6-((triphenylsilyl)oxy)octanal Structure

(3S,4S,5R,6R)-4...

~%

EPOTHILONE C Structure

(3R,4R,5S)-3-(2-(1,3-dithian-2-yl)propan-2-yl)-5-((S)-4-methoxybut-3-en-2-yl)-4,7,7,8,8-pentamethyl-1,1,1-triphenyl-2,6-dioxa-1,7-disilanonane Structure

(3R,4R,5S)-3-(2...

~%

EPOTHILONE C Structure

(4S,6R,7R,8S,9S,16S,Z)-8-((tert-butyldimethylsilyl)oxy)-4-hydroxy-5,5,7,9-tetramethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-6-((triphenylsilyl)oxy)oxacyclohexadec-13-en-2-one Structure

(4S,6R,7R,8S,9S...

~%

EPOTHILONE C Structure

(S,E)-4-(3-(methoxymethoxy)-2-methyl-6-(trimethylsilyl)hex-1-en-5-yn-1-yl)-2-methylthiazole Structure

(S,E)-4-(3-(met...

~%

EPOTHILONE C Structure

(1E,3S,5Z,10S,11S,12R,13R)-11-((tert-butyldimethylsilyl)oxy)-2,10,12,14,14-pentamethyl-1-(2-methylthiazol-4-yl)-15-oxo-13-((triphenylsilyl)oxy)pentadeca-1,5-dien-3-yl acetate Structure

(1E,3S,5Z,10S,1...

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

(4S,6R,7S,8S,9S,16S,Z)-8-((tert-butyldimethylsilyl)oxy)-4,6-dihydroxy-5,5,7,9-tetramethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)oxacyclohexadec-13-en-2-one Structure

(4S,6R,7S,8S,9S...

~%

EPOTHILONE C Structure

(4S,6R,7S,8S,9S,16S,Z)-4,8-bis((tert-butyldimethylsilyl)oxy)-6-hydroxy-5,5,7,9-tetramethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)oxacyclohexadec-13-en-2-one Structure

(4S,6R,7S,8S,9S...

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

tert-butyl (3S,5R,6S,7S,8S)-7-((tert-butyldimethylsilyl)oxy)-3,5-dihydroxy-4,4,6,8-tetramethylundec-10-enoate Structure

tert-butyl (3S,...

~%

EPOTHILONE C Structure

tert-butyl (3S,6R,7S,8S)-3,7-bis((tert-butyldimethylsilyl)oxy)-4,4,6,8-tetramethyl-5-oxoundec-10-enoate Structure

tert-butyl (3S,...

~%

EPOTHILONE C Structure

(3R,4R,5S,6S)-5-((tert-butyldimethylsilyl)oxy)-2,2,4,6-tetramethyl-3-((triphenylsilyl)oxy)non-8-enal Structure

(3R,4R,5S,6S)-5...

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

(3S,6R,7S,8S)-tert-butyldimethylsilyl 3,7-bis((tert-butyldimethylsilyl)oxy)-4,4,6,8-tetramethyl-5-oxoundec-10-enoate Structure

(3S,6R,7S,8S)-t...

~%

EPOTHILONE C Structure

(3S,5R,6R,7S,8S)-tert-butyl 7-((tert-butyldimethylsilyl)oxy)-3-hydroxy-4,4,6,8-tetramethyl-5-((triphenylsilyl)oxy)undec-10-enoate Structure

(3S,5R,6R,7S,8S...

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

(6R,7R,8S,9S,16S,Z)-8-((tert-butyldimethylsilyl)oxy)-5,5,7,9-tetramethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-6-((triphenylsilyl)oxy)oxacyclohexadec-13-ene-2,4-dione Structure

(6R,7R,8S,9S,16...

~%

EPOTHILONE C Structure

N/A Structure

~%

EPOTHILONE C Structure

(4S,6R,7R,8S,9S,16S,Z)-8-((tert-butyldimethylsilyl)oxy)-5,5,7,9-tetramethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-4-((triethylsilyl)oxy)-6-((triphenylsilyl)oxy)oxacyclohexadec-13-en-2-one Structure

(4S,6R,7R,8S,9S...

~%

EPOTHILONE C Structure

Total synthesis of epothilone A: the macrolactonization appr...

[Yang; He; Vourloumis; Vallberg; Nicolau Angewandte Chemie - International Edition in English, 1997 , vol. 36, # 1-2 p. 166 - 168]

Alkyne Metathesis: Development of a Novel Molybdenum??Based ...

[Fuerstner, Alois; Mathes, Christian; Lehmann, Christian W. Chemistry - A European Journal, 2001 , vol. 7, # 24 p. 5299 - 5317]

Alkyne Metathesis: Development of a Novel Molybdenum??Based ...

[Fuerstner, Alois; Mathes, Christian; Lehmann, Christian W. Chemistry - A European Journal, 2001 , vol. 7, # 24 p. 5299 - 5317]

Enantioselective total synthesis of epothilones A and B usin...

[Sawada, Daisuke; Kanai, Motomu; Shibasaki, Masakatsu Journal of the American Chemical Society, 2000 , vol. 122, # 43 p. 10521 - 10532]

Enantioselective total synthesis of epothilones A and B usin...

[Sawada, Daisuke; Kanai, Motomu; Shibasaki, Masakatsu Journal of the American Chemical Society, 2000 , vol. 122, # 43 p. 10521 - 10532]