(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol -Drug Synthesis Database

【结构式】

【分子编号】44468

【品名】(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol

【CA登记号】

【分子式】C₂₃H₄₁NO₂SSi

【分子量】423.73558

【元素组成】C 65.19% H 9.75% N 3.31% O 7.55% S 7.57% Si 6.63%

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：(XXVI)

Assembly of the final product: The condensation of SAMP hydrazone (XVII) with 4-(benzyloxy)butyl iodide (XVIII) by means of LDA in THF gives the chiral 2-methylhexanal hydrazone (XIX), which is ozonolyzed in dichloromethane, yielding the free aldehyde (XX). The reduction of (XX) with NaBH4 in methanol affords the corresponding alcohol (XXI), which is protected with Tbdms-Cl and TEA in dichloromethane, providing the silyl ether (XXII). The hydrogenolysis of (XXII) with H2 over Pd/C in THF furnishes the alcohol (XXIII), which is oxidized to the aldehyde (XXIV) with oxalyl chloride, DMSO and TEA in dichloromethane. The condensation of aldehyde (XXIV) with the intermediate phosphonium salt (XVI) by means of NaHMDS in THF gives the silylated diol (XXV), which is selectively monodesilylated with CSA in dichloromethane/methanol to yield the primary alcohol (XXVI). The oxidation of (XXVI) with SO3/pyridine, DMSO and TEA in dichloromethane affords the corresponding aldehyde (XXVII), which is condensed with the oxoacid intermediate (VI) by means of LDA in THF to provide the linear heptadecadienoic acid (XXVIII) as a diastereomeric mixture.

参考文献中间体

合成目标

【1】 Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	43166	(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid	C₁₅H₃₀O₄Si	详情	详情
(XVI)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide	C₃₄H₄₃INOPSSi	详情	详情
(XVII)	44460	N-[(2R)-2-methoxypyrrolidinyl]-N-[(E)propylidene]amine; (2R)-2-methoxy-N-[(E)propylidene]-1-pyrrolidinamine	C₈H₁₆N₂O	详情	详情
(XVIII)	44461	benzyl 4-iodobutyl ether; 1-[(4-iodobutoxy)methyl]benzene	C₁₁H₁₅IO	详情	详情
(XIX)	44462	N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-N-[(2R)-2-methoxypyrrolidinyl]amine; (2R)-N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-2-methoxy-1-pyrrolidinamine	C₁₉H₃₀N₂O₂	详情	详情
(XX)	44463	(2S)-6-(benzyloxy)-2-methylhexanal	C₁₄H₂₀O₂	详情	详情
(XXI)	44464	(2S)-6-(benzyloxy)-2-methyl-1-hexanol	C₁₄H₂₂O₂	详情	详情
(XXII)	44465	benzyl (5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexyl ether; [[(2S)-6-(benzyloxy)-2-methylhexyl]oxy](tert-butyl)dimethylsilane	C₂₀H₃₆O₂Si	详情	详情
(XXIII)	44466	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-1-hexanol	C₁₃H₃₀O₂Si	详情	详情
(XXIV)	43163	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexanal	C₁₃H₂₈O₂Si	详情	详情
(XXV)	44467	4-((1E,3S,5Z,10S)-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-1,5-undecadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienyl ether	C₂₉H₅₅NO₂SSi₂	详情	详情
(XXVI)	44468	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol	C₂₃H₄₁NO₂SSi	详情	详情
(XXVII)	44469	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal	C₂₃H₃₉NO₂SSi	详情	详情
(XXVIII)	44470	(3S,6R,7S,8S,12Z,15S,16E)-3,15-bis[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid	C₃₈H₆₉NO₆SSi₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVI)

参考文献中间体

合成目标

【1】 Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	43166	(3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid	C₁₅H₃₀O₄Si	详情	详情
(XVI)	44459	[(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide	C₃₄H₄₃INOPSSi	详情	详情
(XVII)	44460	N-[(2R)-2-methoxypyrrolidinyl]-N-[(E)propylidene]amine; (2R)-2-methoxy-N-[(E)propylidene]-1-pyrrolidinamine	C₈H₁₆N₂O	详情	详情
(XVIII)	44461	benzyl 4-iodobutyl ether; 1-[(4-iodobutoxy)methyl]benzene	C₁₁H₁₅IO	详情	详情
(XIX)	44462	N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-N-[(2R)-2-methoxypyrrolidinyl]amine; (2R)-N-[(E,2S)-6-(benzyloxy)-2-methylhexylidene]-2-methoxy-1-pyrrolidinamine	C₁₉H₃₀N₂O₂	详情	详情
(XX)	44463	(2S)-6-(benzyloxy)-2-methylhexanal	C₁₄H₂₀O₂	详情	详情
(XXI)	44464	(2S)-6-(benzyloxy)-2-methyl-1-hexanol	C₁₄H₂₂O₂	详情	详情
(XXII)	44465	benzyl (5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexyl ether; [[(2S)-6-(benzyloxy)-2-methylhexyl]oxy](tert-butyl)dimethylsilane	C₂₀H₃₆O₂Si	详情	详情
(XXIII)	44466	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-1-hexanol	C₁₃H₃₀O₂Si	详情	详情
(XXIV)	43163	(5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-5-methylhexanal	C₁₃H₂₈O₂Si	详情	详情
(XXV)	44467	4-((1E,3S,5Z,10S)-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-1,5-undecadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienyl ether	C₂₉H₅₅NO₂SSi₂	详情	详情
(XXVI)	44468	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol	C₂₃H₄₁NO₂SSi	详情	详情
(XXVII)	44469	(2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal	C₂₃H₃₉NO₂SSi	详情	详情
(XXVIII)	44470	(3S,6R,7S,8S,12Z,15S,16E)-3,15-bis[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8,16-pentamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid	C₃₈H₆₉NO₆SSi₂	详情	详情

Extended Information