isopropyl (3S,5R,6S,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3,5-dihydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate -Drug Synthesis Database

【结构式】

【分子编号】44499

【品名】isopropyl (3S,5R,6S,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3,5-dihydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate

【CA登记号】

【分子式】C₃₈H₅₇NO₇S

【分子量】671.93912

【元素组成】C 67.93% H 8.55% N 2.08% O 16.67% S 4.77%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XXXIII)

Assembly of the target compound: The condensation of intermediates (XVI) and (XXVII) by means of 9-BBN, a Pd catalyst and Cs2CO3 in THF/DMF gives the adduct (XXVIII), which is selectively deprotected with HF/pyridine in THF, yielding the primary alcohol (XXIX). The oxidation of (XXIX) with DMP in dichloromethane affords the aldehyde (XXX), which is condensed with the silyl enol ether (XXXI) by means of TiCl4 in dichloromethane to provide the isopropyl carboxylate (XXXII). The desilylation of (XXXII) with TBAF in THF gives the dihydroxyester (XXXIII), which is selectively monosilylated with Tbdms-Cl and imidazole, yielding the hydroxyester (XXXIV). The oxidation of (XXXIV) with DMP in dichloromethane affords the ketoester (XXXV), which was submitted to a basic hydrolysis of its acetoxy and isopropyl ester groups with NaOH in refluxing methanol to furnish the hydroxyacid (XXXVI).

参考文献中间体

合成目标

【1】 Panek, J.S.; Zhu, B.; Total synthesis of apothilone A. Org Lett 2000, 2, 17, 2575.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XVI)	44487	(5R)-5-[(1R,2S,3S)-2-(benzyloxy)-1,3-dimethyl-5-hexenyl]-2,2,3,3,6,6,9,9,10,10-decamethyl-4,8-dioxa-3,9-disilaundecane; benzyl (1S,2S)-1-((1R,2R)-2,4-bis[[tert-butyl(dimethyl)silyl]oxy]-1,3,3-trimethylbutyl)-2-methyl-4-pentenyl ether	C₃₂H₆₀O₃Si₂	详情	详情
(XXVII)	44493	(1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate	C₁₃H₁₆INO₂S	详情	详情
(XXVIII)	44494	(1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11,13-bis[[tert-butyl(dimethyl)silyl]oxy]-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-tridecenyl acetate	C₄₅H₇₇NO₅SSi₂	详情	详情
(XXIX)	44495	(1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11-[[tert-butyl(dimethyl)silyl]oxy]-13-hydroxy-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-tridecenyl acetate	C₃₉H₆₃NO₅SSi	详情	详情
(XXX)	44496	(1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11-[[tert-butyl(dimethyl)silyl]oxy]-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-13-oxo-3-tridecenyl acetate	C₃₉H₆₁NO₅SSi	详情	详情
(XXXI)	44497	1-isopropoxyvinyl trimethylsilyl ether; [(1-isopropoxyvinyl)oxy](trimethyl)silane	C₈H₁₈O₂Si	详情	详情
(XXXII)	44498	isopropyl (3S,5R,6R,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate	C₄₄H₇₁NO₇SSi	详情	详情
(XXXIII)	44499	isopropyl (3S,5R,6S,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3,5-dihydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate	C₃₈H₅₇NO₇S	详情	详情
(XXXIV)	44500	isopropyl (3S,5R,6S,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate	C₄₄H₇₁NO₇SSi	详情	详情
(XXXV)	44501	isopropyl (3S,6R,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate	C₄₄H₆₉NO₇SSi	详情	详情
(XXXVI)	44502	(3S,6R,7S,8S,12Z,15S,16E)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid	C₃₉H₆₁NO₆SSi	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXXIII)

参考文献中间体

合成目标

【1】 Panek, J.S.; Zhu, B.; Total synthesis of apothilone A. Org Lett 2000, 2, 17, 2575.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XVI)	44487	(5R)-5-[(1R,2S,3S)-2-(benzyloxy)-1,3-dimethyl-5-hexenyl]-2,2,3,3,6,6,9,9,10,10-decamethyl-4,8-dioxa-3,9-disilaundecane; benzyl (1S,2S)-1-((1R,2R)-2,4-bis[[tert-butyl(dimethyl)silyl]oxy]-1,3,3-trimethylbutyl)-2-methyl-4-pentenyl ether	C₃₂H₆₀O₃Si₂	详情	详情
(XXVII)	44493	(1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate	C₁₃H₁₆INO₂S	详情	详情
(XXVIII)	44494	(1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11,13-bis[[tert-butyl(dimethyl)silyl]oxy]-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-tridecenyl acetate	C₄₅H₇₇NO₅SSi₂	详情	详情
(XXIX)	44495	(1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11-[[tert-butyl(dimethyl)silyl]oxy]-13-hydroxy-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-tridecenyl acetate	C₃₉H₆₃NO₅SSi	详情	详情
(XXX)	44496	(1S,3Z,8S,9S,10R,11R)-9-(benzyloxy)-11-[[tert-butyl(dimethyl)silyl]oxy]-8,10,12,12-tetramethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-13-oxo-3-tridecenyl acetate	C₃₉H₆₁NO₅SSi	详情	详情
(XXXI)	44497	1-isopropoxyvinyl trimethylsilyl ether; [(1-isopropoxyvinyl)oxy](trimethyl)silane	C₈H₁₈O₂Si	详情	详情
(XXXII)	44498	isopropyl (3S,5R,6R,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate	C₄₄H₇₁NO₇SSi	详情	详情
(XXXIII)	44499	isopropyl (3S,5R,6S,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3,5-dihydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate	C₃₈H₅₇NO₇S	详情	详情
(XXXIV)	44500	isopropyl (3S,5R,6S,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-12,16-heptadecadienoate	C₄₄H₇₁NO₇SSi	详情	详情
(XXXV)	44501	isopropyl (3S,6R,7S,8S,12Z,15S,16E)-15-(acetoxy)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate	C₄₄H₆₉NO₇SSi	详情	详情
(XXXVI)	44502	(3S,6R,7S,8S,12Z,15S,16E)-7-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid	C₃₉H₆₁NO₆SSi	详情	详情

Extended Information