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【结 构 式】

【分子编号】40831

【品名】(7S,10R,11S,12S,16Z,19S)-7-[[tert-butyl(dimethyl)silyl]oxy]-11-hydroxy-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one

【CA登记号】

【 分 子 式 】C45H87NO5SSi3

【 分 子 量 】838.51202

【元素组成】C 64.46% H 10.46% N 1.67% O 9.54% S 3.82% Si 10.05%

与该中间体有关的原料药合成路线共 6 条

合成路线1

该中间体在本合成路线中的序号:(XX)

The silylation of 3(S)-hydroxytetrahydrofuran-2-one (I) with TBDMS-Cl and imidazole gives the silyl ether (II), which is methylated with MeLi in THF yields the 3(S)-(TBDMSO)-5-hydroxy-2-pentanone (IV), through the hemiketal intermediate (III). Simultaneously, the cyclization of 1,3-dichloropropanone (V) with thioacetamide (VI) in refluxing ethanol affords 4-(chloromethyl)-2-methylthiazole (VII), which is treated with tributylphosphine to provide the phosphonium salt (VIII). The condensation of (VIII) with the ketone (IV) gives the unsaturated alcohol (IX), which is oxidized to the corresponding aldehyde (X) by means of oxalyl chloride in DMSO. The condensation of (X) with 2-phosphonopropionic acid triethyl ester (XI) by means of KHMDS gives the dienoic acid ethyl ester (XII), which is reduced with DIBAL in THF yielding the corresponding primary alcohol (XIII). The condensation of (XIII) with the chiral sulfone intermediate (XIV) by means of KHMDS and PPh3 affords the corresponding adduct (XV), which is desulfurized with Na/Hg in THF/methanol giving the silylated diol (XVI). The selective monodesilylation of (XVI) with CSA in methanol/dichloromethane yields the primary alcohol (XVII), which is oxidized with Dess Martin periodinane (DMP) to the aldehyde (XVIII). The condensation of (XVIII) with the intermediate chiral ketone (XIX) by means of LDA in THF affords the hydroxy ketone (XX).

1 Mulzer, J.; Ohler, E.; Mantoulidis, A. (Schering AG); Method for producing epothilone B and derivs., and intermediate products for this method. WO 0023452 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 40815 (3S)-3-hydroxydihydro-2(3H)-furanone 19444-84-9 C4H6O3 详情 详情
(II) 40816 (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]dihydro-2(3H)-furanone C10H20O3Si 详情 详情
(III) 40817 (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyltetrahydro-2-furanol C11H24O3Si 详情 详情
(IV) 40818 (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-2-pentanone C11H24O3Si 详情 详情
(V) 63907 1,3-dichloroacetone C3H4Cl2O 详情 详情
(VI) 19170 ethanethioamide 62-55-5 C2H5NS 详情 详情
(VII) 40819 4-(chloromethyl)-2-methyl-1,3-thiazole C5H6ClNS 详情 详情
(VIII) 40820 tributyl[(2-methyl-1,3-thiazol-4-yl)methyl]phosphonium chloride C17H33ClNPS 详情 详情
(IX) 40821 (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-penten-1-ol C16H29NO2SSi 详情 详情
(X) 40822 (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal C16H27NO2SSi 详情 详情
(XI) 18816 ethyl 2-(diethoxyphosphoryl)propanoate 3699-66-9 C9H19O5P 详情 详情
(XII) 40823 ethyl (2Z,5S,6E)-5-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-7-(2-methyl-1,3-thiazol-4-yl)-2,6-heptadienoate C21H35NO3SSi 详情 详情
(XIII) 40824 (2Z,5S,6E)-5-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-7-(2-methyl-1,3-thiazol-4-yl)-2,6-heptadien-1-ol C19H33NO2SSi 详情 详情
(XIV) 40825 tert-butyl(dimethyl)[[(2S)-2-methyl-4-(phenylsulfonyl)butyl]oxy]silane; (3S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methylbutyl phenyl sulfone C17H30O3SSi 详情 详情
(XV) 40826 (1R,3Z,6S,7E)-6-[[tert-butyl(dimethyl)silyl]oxy]-1-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-3,7-dimethyl-8-(2-methyl-1,3-thiazol-4-yl)-3,7-octadienyl phenyl sulfone; 4-[(1E,3S,5Z,8R,10S)-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-8-(phenylsulfonyl)-1,5-undecadienyl]-2-methyl-1,3-thiazole C36H61NO4S2Si2 详情 详情
(XVI) 40827 tert-butyl(dimethyl)silyl (1S,3Z,8S)-9-[[tert-butyl(dimethyl)silyl]oxy]-4,8-dimethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-nonenyl ether; 4-((1E,3S,5Z,10S)-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-1,5-undecadienyl)-2-methyl-1,3-thiazole C30H57NO2SSi2 详情 详情
(XVII) 40828 (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol C24H43NO2SSi 详情 详情
(XVIII) 40829 (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal C24H41NO2SSi 详情 详情
(XIX) 40830 (5S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-3-heptanone C21H46O3Si2 详情 详情
(XX) 40831 (7S,10R,11S,12S,16Z,19S)-7-[[tert-butyl(dimethyl)silyl]oxy]-11-hydroxy-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one C45H87NO5SSi3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XX)

The silylation of the OH group of (XX) with TBDMS-triflate gives the fully silylated ketone (XXI), which is selectively monodesilylated with CSA in methanol/dichloromethane affording the primary alcohol (XXII). Oxidation of (XXII) first with Dess Martin periodinane (DMP) and then with NaClO2 provides the corresponding carboxylic acid (XXIII), which is again selectively desilylated with TBAF in THF to give the 15-hydroxy-5-oxoheptadecadienoic acid (XXIV). The cyclization of (XXIV) by means of DEC and DMAP in chloroform yields fully silylated Epothilon D (XXV), which is desilylated with HF/pyridine in THF to afford Epothilon D (XXVI). Finally, this compound is epoxidized with MCPBA in chloroform to afford the target Epothilon B.

1 Mulzer, J.; Ohler, E.; Mantoulidis, A. (Schering AG); Method for producing epothilone B and derivs., and intermediate products for this method. WO 0023452 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XX) 40831 (7S,10R,11S,12S,16Z,19S)-7-[[tert-butyl(dimethyl)silyl]oxy]-11-hydroxy-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one C45H87NO5SSi3 详情 详情
(XXI) 40832 (7S,10R,11S,12S,16Z,19S)-7,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one C51H101NO5SSi4 详情 详情
(XXII) 40833 (5S,8R,9S,10S,14Z,17S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,10,14,19,19,20,20-tridecamethyl-17-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,18-dioxa-3,19-disila-14-henicosen-7-one C45H87NO5SSi3 详情 详情
(XXIII) 40834 (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid C45H85NO6SSi3 详情 详情
(XXIV) 40835 (3S,6R,7S,8S,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid C39H71NO6SSi2 详情 详情
(XXV) 40836 (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione C39H69NO5SSi2 详情 详情
(XXVI) 40837 (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione C27H41NO5S 详情 详情

合成路线3

该中间体在本合成路线中的序号:(XXIX)

The enantioselective condensation of 3-(tert-butyldimethylsilyloxy)propanal (XX) with ketene acetal (XXI) catalyzed by N-tosyl-D-valine and BH3/THF gives the beta-hydroxyester (XXII), which is silylated with Tbdms-OTf, yielding the bis-silyl ether (XXIII). The reduction of (XXIII) with DIBAL in toluene affords the carbinol (XXIV), which is oxidized to the corresponding aldehyde (XXV) with DMP in dichloromethane. The Grignard condensation of (XXV) with Et-MgBr in ethyl ether gives the secondary alcohol (XXVI), which is oxidized with DMP as before to yield the ketone (XXVII). Alternatively, the silylated ester (XXIII) can be treated with Tms-CH2-Li in pentane/methanol to give the methyl ketone (XXVIII), which is methylated again with MeI and LDA in THF to afford the ketone (XXVII). The condensation of ketone (XXVII) with the intermediate carbaldehyde (XIX) by means of BuLi in THF gives the adduct (XXIX), which is silylated with Tbdms-OTf, yielding the fully silylated compound (XXX). The selective monodesilylation of (XXX) with CSA in MeOH/dichloromethane affords the primary alcohol (XXXI), which is oxidized with DMP and NaClO2 to provide the carboxylic acid (XXXII).

1 Mulzer, J.; et al.; Total synthesis of epothilones B and D. J Org Chem 2000, 65, 22, 7456.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIX) 40829 (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal C24H41NO2SSi 详情 详情
(XX) 45546 3-[[tert-butyl(dimethyl)silyl]oxy]propanal 570-24-1 C9H20O2Si 详情 详情
(XXI) 42016 1-Methoxy-2-methyl-1-(trimethylsiloxy)propene;1-Methoxy-2,2-dimethyl-1-(trimethylsiloxy)ethene;1-Methoxy-1-(trimethylsilyloxy)-2-methylpropene;[(1-methoxy-2-methyl-1-propenyl)oxy](trimethyl)silane; 1-methoxy-2-methyl-1-propenyl trimethylsilyl ether ;dimethylketene methyl trimethylsilyl acetal 31469-15-5 C8H18O2Si 详情 详情
(XXII) 40843 methyl (3S)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-2,2-dimethylpentanoate C14H30O4Si 详情 详情
(XXIII) 40844 methyl (3S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2-dimethylpentanoate C20H44O4Si2 详情 详情
(XXIV) 40845 (3S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2-dimethyl-1-pentanol C19H44O3Si2 详情 详情
(XXV) 40846 (3S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2-dimethylpentanal C19H42O3Si2 详情 详情
(XXVI) 40847 (5S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-3-heptanol C21H48O3Si2 详情 详情
(XXVII) 40830 (5S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-3-heptanone C21H46O3Si2 详情 详情
(XXVIII) 46137 (4S)-4,6-bis[[tert-butyl(dimethyl)silyl]oxy]-3,3-dimethyl-2-hexanone C20H44O3Si2 详情 详情
(XXIX) 40831 (7S,10R,11S,12S,16Z,19S)-7-[[tert-butyl(dimethyl)silyl]oxy]-11-hydroxy-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one C45H87NO5SSi3 详情 详情
(XXX) 40832 (7S,10R,11S,12S,16Z,19S)-7,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one C51H101NO5SSi4 详情 详情
(XXXI) 40833 (5S,8R,9S,10S,14Z,17S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,10,14,19,19,20,20-tridecamethyl-17-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,18-dioxa-3,19-disila-14-henicosen-7-one C45H87NO5SSi3 详情 详情
(XXXII) 40834 (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid C45H85NO6SSi3 详情 详情

合成路线4

该中间体在本合成路线中的序号:(XVIII)

The allylation of 2-(2-methylthiazol-4-ylmethylene)propionaldehyde (X) with allyl(diisopinocampheyl)borane gives the chiral secondary alcohol (XI), which is protected with Tbdms-Cl, yielding the silyl ether (XII). The oxidation of the terminal double bond of (XII) with OsO4 and NaIO4 affords the chiral aldehyde (XIII), which is condensed with the intermediate iodovinyl compound (IX) by means of Ni/Cr to provide the allyl alcohol derivative (XIV). The reaction of (XIV) with SOCl2 gives the rearranged chloromethyl compound (XV), which is treated with LiEt3BH to cleave the oxazolidine chiral auxiliary and dechlorinate the chloromethyl group, yielding the primary alcohol (XVI). The controlled oxidation of the OH group of (XVI) with PCC affords the aldehyde (XVII), which is submitted to an aldol condensation with the intermediate ketone (VI) by means of LDA to provide the aldol (XVIII). The protection of the OH group of (XVIII) with Tbdms-Cl gives the fully silylated compound (XIX), which is regioselectively monodesilylated with camphorsulfonic acid (CSA) to yield the primary alcohol (XX).

1 Chen, Y.; Taylor, R.E.; Total synthesis of epothilones B and D. Org Lett 2001, 3, 14, 2221.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI) 40830 (5S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-3-heptanone C21H46O3Si2 详情 详情
(IX) 52569 3-(6-iodo-2-methyl-6-heptenoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one C18H22INO3 详情 详情
(X) 44456 (E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal C8H9NOS 详情 详情
(XI) 43171 (1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol C11H15NOS 详情 详情
(XII) 44444 4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether C17H29NOSSi 详情 详情
(XIII) 40822 (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal C16H27NO2SSi 详情 详情
(XIV) 52571 3-[9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-7-hydroxy-2,10-dimethyl-6-methylidene-11-(2-methyl-1,3-thiazol-4-yl)-10-undecenoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one C34H50N2O5SSi 详情 详情
(XV) 52570 3-[6-(chloromethyl)-9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one C34H49ClN2O4SSi 详情 详情
(XVI) 40828 (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol C24H43NO2SSi 详情 详情
(XVII) 40829 (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal C24H41NO2SSi 详情 详情
(XVIII) 40831 (7S,10R,11S,12S,16Z,19S)-7-[[tert-butyl(dimethyl)silyl]oxy]-11-hydroxy-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one C45H87NO5SSi3 详情 详情
(XIX) 40832 (7S,10R,11S,12S,16Z,19S)-7,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one C51H101NO5SSi4 详情 详情
(XX) 40833 (5S,8R,9S,10S,14Z,17S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,10,14,19,19,20,20-tridecamethyl-17-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,18-dioxa-3,19-disila-14-henicosen-7-one C45H87NO5SSi3 详情 详情

合成路线5

该中间体在本合成路线中的序号:(XXIX)

Assembly of the target compound: The enantioselective condensation of 3-(tert-butyldimethylsilyloxy)propanal (XX) with ketene acetal (XXI) catalyzed by N-tosyl-D-valine and BH3/THF gives the beta-hydroxyester (XXII), which is silylated with Tbdms-OTf, yielding the bis-silyl ether (XXIII). The reduction of (XXIII) with DIBAL in toluene affords the carbinol (XXIV), which is oxidized to the corresponding aldehyde (XXV) with DMP in dichloromethane. The Grignard condensation of (XXV) with Et-MgBr in ethyl ether gives the secondary alcohol (XXVI), which is oxidized with DMP as before to yield the ketone (XXVII). Alternatively, the silylated ester (XXIII) can be treated with Tms-CH2-Li in pentane/methanol to give the methyl ketone (XXVIII), which is methylated again with MeI and LDA in THF to afford the ketone (XXVII). The condensation of ketone (XXVII) with the intermediate carbaldehyde (XIX) by means of BuLi in THF gives the adduct (XXIX), which is silylated with Tbdms-OTf, yielding the fully silylated compound (XXX). The selective monodesilylation of (XXX) with CSA in MeOH/dichloromethane affords the primary alcohol (XXXI), which is oxidized with DMP and NaClO2 to provide the carboxylic acid (XXXII).

1 Mulzer, J.; et al.; Total synthesis of epothilones B and D. J Org Chem 2000, 65, 22, 7456.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIX) 40829 (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal C24H41NO2SSi 详情 详情
(XX) 45546 3-[[tert-butyl(dimethyl)silyl]oxy]propanal 570-24-1 C9H20O2Si 详情 详情
(XXI) 42016 1-Methoxy-2-methyl-1-(trimethylsiloxy)propene;1-Methoxy-2,2-dimethyl-1-(trimethylsiloxy)ethene;1-Methoxy-1-(trimethylsilyloxy)-2-methylpropene;[(1-methoxy-2-methyl-1-propenyl)oxy](trimethyl)silane; 1-methoxy-2-methyl-1-propenyl trimethylsilyl ether ;dimethylketene methyl trimethylsilyl acetal 31469-15-5 C8H18O2Si 详情 详情
(XXII) 40843 methyl (3S)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-2,2-dimethylpentanoate C14H30O4Si 详情 详情
(XXIII) 40844 methyl (3S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2-dimethylpentanoate C20H44O4Si2 详情 详情
(XXIV) 40845 (3S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2-dimethyl-1-pentanol C19H44O3Si2 详情 详情
(XXV) 40846 (3S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2-dimethylpentanal C19H42O3Si2 详情 详情
(XXVI) 40847 (5S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-3-heptanol C21H48O3Si2 详情 详情
(XXVII) 40830 (5S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-3-heptanone C21H46O3Si2 详情 详情
(XXVIII) 46137 (4S)-4,6-bis[[tert-butyl(dimethyl)silyl]oxy]-3,3-dimethyl-2-hexanone C20H44O3Si2 详情 详情
(XXIX) 40831 (7S,10R,11S,12S,16Z,19S)-7-[[tert-butyl(dimethyl)silyl]oxy]-11-hydroxy-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one C45H87NO5SSi3 详情 详情
(XXX) 40832 (7S,10R,11S,12S,16Z,19S)-7,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one C51H101NO5SSi4 详情 详情
(XXXI) 40833 (5S,8R,9S,10S,14Z,17S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,10,14,19,19,20,20-tridecamethyl-17-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,18-dioxa-3,19-disila-14-henicosen-7-one C45H87NO5SSi3 详情 详情
(XXXII) 40834 (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid C45H85NO6SSi3 详情 详情

合成路线6

该中间体在本合成路线中的序号:(XVIII)

The allylation of 2-(2-methylthiazol-4-ylmethylene)propionaldehyde (X) with allyl(diisopinocampheyl)borane gives the chiral secondary alcohol (XI), which is protected with Tbdms-Cl, yielding the silyl ether (XII). The oxidation of the terminal double bond of (XII) with OsO4 and NaIO4 affords the chiral aldehyde (XIII), which is condensed with the intermediate iodovinyl compound (IX) by means of Ni/Cr to provide the allyl alcohol derivative (XIV). The reaction of (XIV) with SOCl2 gives the rearranged chloromethyl compound (XV), which is treated with LiEt3BH to cleave the oxazolidine chiral auxiliary and dechlorinate the chloromethyl group, yielding the primary alcohol (XVI). The controlled oxidation of the OH group of (XVI) with PCC affords the aldehyde (XVII), which is submitted to an aldol condensation with the intermediate ketone (VI) by means of LDA to provide the aldol (XVIII). The protection of the OH group of (XVIII) with Tbdms-Cl gives the fully silylated compound (XIX), which is regioselectively monodesilylated with camphorsulfonic acid (CSA) to yield the primary alcohol (XX).

1 Chen, Y.; Taylor, R.E.; Total synthesis of epothilones B and D. Org Lett 2001, 3, 14, 2221.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI) 40830 (5S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-3-heptanone C21H46O3Si2 详情 详情
(IX) 52569 3-(6-iodo-2-methyl-6-heptenoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one C18H22INO3 详情 详情
(X) 44456 (E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenal C8H9NOS 详情 详情
(XI) 43171 (1E,3S)-2-methyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-hexadien-3-ol C11H15NOS 详情 详情
(XII) 44444 4-((1E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1,5-hexadienyl)-2-methyl-1,3-thiazole; tert-butyl(dimethyl)silyl (1S)-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl ether C17H29NOSSi 详情 详情
(XIII) 40822 (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenal C16H27NO2SSi 详情 详情
(XIV) 52571 3-[9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-7-hydroxy-2,10-dimethyl-6-methylidene-11-(2-methyl-1,3-thiazol-4-yl)-10-undecenoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one C34H50N2O5SSi 详情 详情
(XV) 52570 3-[6-(chloromethyl)-9-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,10-dimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one C34H49ClN2O4SSi 详情 详情
(XVI) 40828 (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol C24H43NO2SSi 详情 详情
(XVII) 40829 (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal C24H41NO2SSi 详情 详情
(XVIII) 40831 (7S,10R,11S,12S,16Z,19S)-7-[[tert-butyl(dimethyl)silyl]oxy]-11-hydroxy-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one C45H87NO5SSi3 详情 详情
(XIX) 40832 (7S,10R,11S,12S,16Z,19S)-7,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one C51H101NO5SSi4 详情 详情
(XX) 40833 (5S,8R,9S,10S,14Z,17S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,10,14,19,19,20,20-tridecamethyl-17-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,18-dioxa-3,19-disila-14-henicosen-7-one C45H87NO5SSi3 详情 详情
Extended Information