220889-44-1

Upstream product

• 78186-80-8 3,3-dimethyl-4-oxohex-1-ene 
• 186417-90-3 (2R,5S)-5-hydroxy-2-[(2S,4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-4,4-dimethyloct-7-en-3-one 
• 186417-88-9 (-)-(5R,6S,7S)-6-hydroxy-8-[(4-methoxybenzyl)oxy]-3,3,5,7-tetramethyloct-1-en-4-one 
• 186417-89-0 (R)-4-[(2S,4S,5S)-2-(4-Methoxy-phenyl)-5-methyl-[1,3]dioxan-4-yl]-2,2-dimethyl-3-oxo-pentanal 
• 186417-92-5 (+)-(2R)-2-[(2S,4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-4,4-dimethylhex-5-en-3-one 
• 105-13-5 4-Methoxybenzyl alcohol 
• 136320-64-4 (2R)-3-[(4-methoxybenzyl)oxy]-2-methylpropanol 
• 132969-71-2 methyl (2S)-[(4-methoxybenzyl)oxy]-2-methylpropanoate 
• 132969-60-9 (2S)-3-[(4-methoxybenzyl)oxy]-2-methylpropanal 
• 106921-60-2 2,2-dimethyl-3-oxopentanal 
• 69739-34-0 t-butyldimethylsiyl triflate 
• 186417-93-6 (-)-(2R,5S)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-[(2S,4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-4,4-dimethyloct-7-en-3-one 
• 187283-44-9 (5S)-5-(tert-butyl-dimethyl-silanyloxy)-4,4-dimethyloct-7en-3-one 

Downstream Products

• 220889-46-3 (2S,3S,4R,7S)-3,7-Bis-(tert-butyl-dimethyl-silanyloxy)-1-(4-methoxy-benzyloxy)-2,4,6,6-tetramethyl-dec-9-en-5-one 
• 350493-51-5 (3S,6R,7S,8S)-3,7-Bis-(tert-butyl-dimethyl-silanyloxy)-9-(4-methoxy-benzyloxy)-4,4,6,8-tetramethyl-5-oxo-nonanoic acid 2-trimethylsilanyl-ethyl ester 
• 220889-48-5 (3S,6R,7S,8S)-3,7-Bis-(tert-butyl-dimethyl-silanyloxy)-9-(4-methoxy-benzyloxy)-4,4,6,8-tetramethyl-5-oxo-nonanoic acid methyl ester 
• 220889-47-4 (3S,6R,7S,8S)-3,7-Bis-(tert-butyl-dimethyl-silanyloxy)-9-(4-methoxy-benzyloxy)-4,4,6,8-tetramethyl-5-oxo-nonanoic acid 
• 220889-58-7 (3S,6R,7S,8S)-3,7-Bis-(tert-butyl-dimethyl-silanyloxy)-9-(4-methoxy-benzyloxy)-4,4,6,8-tetramethyl-5-oxo-nonanal 
• 189453-10-9 epothilone D 
• 152044-54-7 epothilone B 

Relevant academic research and scientific papers

Total synthesis of epothilone B, epothilone D, and cis- and trans-9,10-dehydroepothilone D

The phosphonium salt 35, representing one of the two principal subunits of the epothilones, was prepared from propargyl alcohol via heptenone 22. A Wittig reaction of the phosphorane from 35 with aldehyde 33, obtained from aldol condensation of ketone 27 with aldehyde 28, afforded 37. Seco acid 42 derived from 37 underwent lactonization to give cis-9,10-dehydroepothilone D (43) which was selectively reduced with diimide to yield epothilone D (4) and, after epoxidation, epothilone B (2). An alternative route to epothilone D employed alkyne 39, obtained from 33, in a Castro-Stephens reaction with allylic bromide 34 to furnish enyne 40. The latter was semi-hydrogenated to provide 37. Alkyne 46, prepared from alcohol 45, was converted to trans-vinylstannane 47 which, in a Stille coupling with allylic chloride 50, gave 51. Seco acid 52 derived from 51 underwent lactonization to give trans-9,10-dehydroepothilone D (54). Bioassay data comparing the antiproliferative activity and tubulin polymerization of 43 and 54 with epothilone B (2), epothilone D (4), and paclitaxel (7) showed that the synthetic analogues were less potent than their natural counterparts, although both retain full antiproliferative activity against a paclitaxel-resistant cell line. No significant difference in potency was noted between cis analogue 43 and its trans isomer 54.

Total Syntheses of Epothilones B and D

Total syntheses of the microtubule stabilizing antitumor drugs epothilone B and D are described, starting from optically pure (S)-malic acid and methyl (R)-3-hydroxy-2-methylpropionate. The synthesis is highly convergent by coupling the three fragments C1-C6 (fragment D), C7-C10 (fragment C), and C11-C21 (fragment B). Key steps are two stereoselective Wittig type olefinations to generate the 12,13- and 16,17-double bonds, an enantioselective Mukaiyama aldol addition to synthesize fragment D, and a sulfone anion allyl iodide alkylation to connect fragments B and C. Finally fragment D was attached to the B + C fragment via aldol addition.