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【结 构 式】 
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【分子编号】51447 【品名】(2S,6Z,9S)-10-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decen-1-ol 【CA登记号】 |
【 分 子 式 】C24H52O4SSi 【 分 子 量 】464.82598 【元素组成】C 62.02% H 11.28% O 13.77% S 6.9% Si 6.04% |
合成路线1
该中间体在本合成路线中的序号：(XXIII)Synthesis of the target epothilone: The condensation of the iodinated dioxolane (XI) with the phenylsulfone (XII) by means of BuLi and DMPU gives the adduct (XIII), which is deprotected with Amberlyst 15 to yield the diol (XIV). Regioselective silylation of (XIV) with Tbdms-Cl and imidazole affords the monosilylated diol (XV), which is fully protected with Sem-Cl and DIEA, providing compound (XVI). The reaction of (XVI) with tributyltin hydride gives the stannane (XVII), which is condensed with the chiral aldehyde (XVIII) by means of SnBr4 to yield the 4-decanol derivative (XIX). The elimination of The OH group of (XIX) is performed via its reaction with Cl-C(S)-OPh (XX) to afford the thiocarbonate (XXI), which is then treated with tributyltin hydride to provide the dehydroxylated compound (XXII). Selective deprotection of (XXII) with DDQ gives the primary alcohol (XXIII), which is esterified with pivaloyl chloride, yielding the pivaloyl ester (XXIV). The selective desilylation of the Tbdms group of (XXIV) with TBAF gives the primary alcohol (XXV), which is oxidized to the corresponding aldehyde (XXVI) by means of DMP. The Grignard reaction of aldehyde (XXVI) with methylmagnesium bromide yields the secondary alcohol (XXVII).
| 【1】 Martin, N.; Thomas, E.J.; Total syntheses of epothilones B and D: Applications of allylstannanes in organic synthesis. Tetrahedron Lett 2001, 42, 47, 8373. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 51436 | (4R)-4-(iodomethyl)-2,2-dimethyl-1,3-dioxolane | C6H11IO2 | 详情 | 详情 | |
| (XII) | 51457 | (8S,10Z,15S,16S,17R,20S)-16-[[tert-butyl(dimethyl)silyl]oxy]-20-(2-hydroxyethyl)-2,2,11,15,17,19,19,22,22,23,23-undecamethyl-8-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-5,7,21-trioxa-2lambda(4)-thia-22-sila-10-tetracosen-18-one | C45H87NO6S2Si2 | 详情 | 详情 | |
| (XIII) | 51438 | 1-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-methyl-2-propenyl phenyl sulfone; (4S)-2,2-dimethyl-4-[3-methyl-2-(phenylsulfonyl)-3-butenyl]-1,3-dioxolane | C16H22O4S | 详情 | 详情 | |
| (XIV) | 51439 | (2S)-5-methyl-4-(phenylsulfonyl)-5-hexene-1,2-diol | C13H18O4S | 详情 | 详情 | |
| (XV) | 51440 | (2S)-1-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-4-(phenylsulfonyl)-5-hexen-2-ol | C19H32O4SSi | 详情 | 详情 | |
| (XVI) | 51441 | 1-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]propyl)-2-methyl-2-propenyl phenyl sulfone; (8S)-2,2,11,11,12,12-hexamethyl-8-[3-methyl-2-(phenylsulfonyl)-3-butenyl]-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C25H46O5S2Si | 详情 | 详情 | |
| (XVII) | 51442 | tert-butyl(dimethyl)silyl (2S,4E)-5-methyl-6-(tributylstannyl)-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-4-hexenyl ether; (8S)-2,2,11,11,12,12-hexamethyl-8-[(E)-3-methyl-4-(tributylstannyl)-2-butenyl]-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C31H68O3SSiSn | 详情 | 详情 | |
| (XVIII) | 51443 | (3S)-4-[(4-methoxybenzyl)oxy]-3-methylbutanal | C13H18O3 | 详情 | 详情 | |
| (XIX) | 51444 | (8S,10Z,15S)-8-([[tert-butyl(dimethyl)silyl]oxy]methyl)-18-(4-methoxyphenyl)-2,2,11,15-tetramethyl-5,7,17-trioxa-2lambda(4)-thia-10-octadecen-13-ol | C32H60O6SSi | 详情 | 详情 | |
| (XX) | 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 |
| (XXI) | 51445 | O-((Z,6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-1-[(2S)-3-[(4-methoxybenzyl)oxy]-2-methylpropyl]-3-methyl-6-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-3-heptenyl) O-phenyl carbonothioate | C39H64O7S2Si | 详情 | 详情 | |
| (XXII) | 51446 | tert-butyl(dimethyl)silyl (2S,4Z,9S)-10-[(4-methoxybenzyl)oxy]-5,9-dimethyl-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-4-decenyl ether; (8S)-8-[(Z,7S)-8-[(4-methoxybenzyl)oxy]-3,7-dimethyl-2-octenyl]-2,2,11,11,12,12-hexamethyl-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C32H60O5SSi | 详情 | 详情 | |
| (XXIII) | 51447 | (2S,6Z,9S)-10-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decen-1-ol | C24H52O4SSi | 详情 | 详情 | |
| (XXIV) | 51448 | (2S,6Z,9S)-10-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C29H60O5SSi | 详情 | 详情 | |
| (XXV) | 51449 | (2S,6Z,9S)-10-hydroxy-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C23H46O5S | 详情 | 详情 | |
| (XXVI) | 51450 | (2S,6Z,9S)-2,6-dimethyl-10-oxo-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C23H44O5S | 详情 | 详情 | |
| (XXVII) | 51451 | (2S,6Z,9S)-10-hydroxy-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-undecenyl pivalate | C24H48O5S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIII)Synthesis of the target epothilone: The condensation of the iodinated dioxolane (XI) with the phenylsulfone (XII) by means of BuLi and DMPU gives the adduct (XIII), which is deprotected with Amberlyst 15 to yield the diol (XIV). Regioselective silylation of (XIV) with Tbdms-Cl and imidazole affords the monosilylated diol (XV), which is fully protected with Sem-Cl and DIEA, providing compound (XVI). The reaction of (XVI) with tributyltin hydride gives the stannane (XVII), which is condensed with the chiral aldehyde (XVIII) by means of SnBr4 to yield the 4-decanol derivative (XIX). The elimination of The OH group of (XIX) is performed via its reaction with Cl-C(S)-OPh (XX) to afford the thiocarbonate (XXI), which is then treated with tributyltin hydride to provide the dehydroxylated compound (XXII). Selective deprotection of (XXII) with DDQ gives the primary alcohol (XXIII), which is esterified with pivaloyl chloride, yielding the pivaloyl ester (XXIV). The selective desilylation of the Tbdms group of (XXIV) with TBAF gives the primary alcohol (XXV), which is oxidized to the corresponding aldehyde (XXVI) by means of DMP. The Grignard reaction of aldehyde (XXVI) with methylmagnesium bromide yields the secondary alcohol (XXVII).
| 【1】 Martin, N.; Thomas, E.J.; Total syntheses of epothilones B and D: Applications of allylstannanes in organic synthesis. Tetrahedron Lett 2001, 42, 47, 8373. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 51436 | (4R)-4-(iodomethyl)-2,2-dimethyl-1,3-dioxolane | C6H11IO2 | 详情 | 详情 | |
| (XII) | 51457 | (8S,10Z,15S,16S,17R,20S)-16-[[tert-butyl(dimethyl)silyl]oxy]-20-(2-hydroxyethyl)-2,2,11,15,17,19,19,22,22,23,23-undecamethyl-8-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-5,7,21-trioxa-2lambda(4)-thia-22-sila-10-tetracosen-18-one | C45H87NO6S2Si2 | 详情 | 详情 | |
| (XIII) | 51438 | 1-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-methyl-2-propenyl phenyl sulfone; (4S)-2,2-dimethyl-4-[3-methyl-2-(phenylsulfonyl)-3-butenyl]-1,3-dioxolane | C16H22O4S | 详情 | 详情 | |
| (XIV) | 51439 | (2S)-5-methyl-4-(phenylsulfonyl)-5-hexene-1,2-diol | C13H18O4S | 详情 | 详情 | |
| (XV) | 51440 | (2S)-1-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-4-(phenylsulfonyl)-5-hexen-2-ol | C19H32O4SSi | 详情 | 详情 | |
| (XVI) | 51441 | 1-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]propyl)-2-methyl-2-propenyl phenyl sulfone; (8S)-2,2,11,11,12,12-hexamethyl-8-[3-methyl-2-(phenylsulfonyl)-3-butenyl]-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C25H46O5S2Si | 详情 | 详情 | |
| (XVII) | 51442 | tert-butyl(dimethyl)silyl (2S,4E)-5-methyl-6-(tributylstannyl)-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-4-hexenyl ether; (8S)-2,2,11,11,12,12-hexamethyl-8-[(E)-3-methyl-4-(tributylstannyl)-2-butenyl]-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C31H68O3SSiSn | 详情 | 详情 | |
| (XVIII) | 51443 | (3S)-4-[(4-methoxybenzyl)oxy]-3-methylbutanal | C13H18O3 | 详情 | 详情 | |
| (XIX) | 51444 | (8S,10Z,15S)-8-([[tert-butyl(dimethyl)silyl]oxy]methyl)-18-(4-methoxyphenyl)-2,2,11,15-tetramethyl-5,7,17-trioxa-2lambda(4)-thia-10-octadecen-13-ol | C32H60O6SSi | 详情 | 详情 | |
| (XX) | 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 |
| (XXI) | 51445 | O-((Z,6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-1-[(2S)-3-[(4-methoxybenzyl)oxy]-2-methylpropyl]-3-methyl-6-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-3-heptenyl) O-phenyl carbonothioate | C39H64O7S2Si | 详情 | 详情 | |
| (XXII) | 51446 | tert-butyl(dimethyl)silyl (2S,4Z,9S)-10-[(4-methoxybenzyl)oxy]-5,9-dimethyl-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-4-decenyl ether; (8S)-8-[(Z,7S)-8-[(4-methoxybenzyl)oxy]-3,7-dimethyl-2-octenyl]-2,2,11,11,12,12-hexamethyl-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C32H60O5SSi | 详情 | 详情 | |
| (XXIII) | 51447 | (2S,6Z,9S)-10-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decen-1-ol | C24H52O4SSi | 详情 | 详情 | |
| (XXIV) | 51448 | (2S,6Z,9S)-10-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C29H60O5SSi | 详情 | 详情 | |
| (XXV) | 51449 | (2S,6Z,9S)-10-hydroxy-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C23H46O5S | 详情 | 详情 | |
| (XXVI) | 51450 | (2S,6Z,9S)-2,6-dimethyl-10-oxo-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C23H44O5S | 详情 | 详情 | |
| (XXVII) | 51451 | (2S,6Z,9S)-10-hydroxy-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-undecenyl pivalate | C24H48O5S | 详情 | 详情 |