|
【结 构 式】 
|
【分子编号】45546 【品名】3-[[tert-butyl(dimethyl)silyl]oxy]propanal 【CA登记号】570-24-1 |
【 分 子 式 】C9H20O2Si 【 分 子 量 】188.3421 【元素组成】C 57.4% H 10.7% O 16.99% Si 14.91% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The intermediate carboxylic acid (XVIII) has been obtained as follows: The aldol condensation of 4-methoxy-alpha-methyl-cinnamaldehyde (I) with the enol ether of 3-pentanone (II) gives the racemic aldol (rac)-(III), which is submitted to an enantioselective retroaldol reaction catalyzed by antibody 38C2, yielding the chiral aldol (3R,4R)-(IV). The reduction of the double bond of (IV) with H2 over Rh/Al2O3 in THF affords the saturated hydroxyketone (V), which is treated with Tbdms-Cl and imidazole to provide the silyl ether (VI). The methylation of (VI) with methyl iodide and LDA in THF gives the isopropyl ketone (VII), which is condensed with aldehyde (VIII) by means of LDA in THF to yield the aldol (IX). The reaction of (IX) with Tbdms-Cl and imidazole affords the tris-silyl ether (X), which is oxidized at the aromatic ring by means of RuCl3 and NaIO4 to provide the aldehyde (XI).
| 【1】 Sinha, S.C.; Barbas, C.F. III; Lerner, R.A.; The antibody catalysis route to the total synthesis of epothilones. Proc Natl Acad Sci USA 1998, 95, 25, 14603. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (rac)-(III) | 45542 | (rac)-(4R*,5R*,6E)-5-hydroxy-7-(4-methoxyphenyl)-4,6-dimethyl-6-hepten-3-one | 2592-19-0 | C16H22O3 | 详情 | 详情 |
| (3R, 4R)-(IV) | 55588 | (4R,5R,6E)-5-hydroxy-7-(4-methoxyphenyl)-4,6-dimethyl-6-hepten-3-one | C16H22O3 | 详情 | 详情 | |
| (I) | 45540 | (E)-3-(4-methoxyphenyl)-2-methyl-2-propenoic acid | C11H12O3 | 详情 | 详情 | |
| (II) | 45541 | (E)-1-ethyl-1-propenyl dibutylborinate | C13H27BO | 详情 | 详情 | |
| (V) | 45543 | (4R,5S,6S)-5-hydroxy-7-(4-methoxyphenyl)-4,6-dimethyl-3-heptanone | 71-44-3 | C16H24O3 | 详情 | 详情 |
| (VI) | 45544 | (4R,5S,6S)-5-[[tert-butyl(dimethyl)silyl]oxy]-7-(4-methoxyphenyl)-4,6-dimethyl-3-heptanone | C22H38O3Si | 详情 | 详情 | |
| (VII) | 45545 | (4R,5S,6S)-5-[[tert-butyl(dimethyl)silyl]oxy]-7-(4-methoxyphenyl)-2,4,6-trimethyl-3-heptanone | C23H40O3Si | 详情 | 详情 | |
| (VIII) | 45546 | 3-[[tert-butyl(dimethyl)silyl]oxy]propanal | 570-24-1 | C9H20O2Si | 详情 | 详情 |
| (IX) | 45547 | (5S,6R,9S)-9-hydroxy-5-[(1S)-2-(4-methoxyphenyl)-1-methylethyl]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disilapentadecan-7-one | 18063-02-0 | C32H60O5Si2 | 详情 | 详情 |
| (X) | 45548 | (5S,6R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-[(1S)-2-(4-methoxyphenyl)-1-methylethyl]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disilapentadecan-7-one | C38H74O5Si3 | 详情 | 详情 | |
| (XI) | 45549 | (3S,4S,5R,8S)-4,8,10-tris[[tert-butyl(dimethyl)silyl]oxy]-3,5,7,7-tetramethyl-6-oxodecanal | C32H68O5Si3 | 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 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3
该中间体在本合成路线中的序号：(I)The ketonic intermediate (VI) has been obtained as follows: The condensation of the 3-(tert-butyldimethylsilyloxy)propionaldehyde (I) with the silylated enol ether (II), catalyzed by the chiral boron reagent (III), gives the phenyl hydroxyester (IV), which is protected with Tbdms-Cl to provide the silyl ether (V). Finally, the Grignard reaction of (V) with Et-MgBr affords the target ketonic intermediate (VI).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 45546 | 3-[[tert-butyl(dimethyl)silyl]oxy]propanal | 570-24-1 | C9H20O2Si | 详情 | 详情 |
| (II) | 52563 | trimethyl{[2-methyl-1-(phenyloxy)-1-propenyl]oxy}silane; 2-methyl-1-(phenyloxy)-1-propenyl trimethylsilyl ether | C13H20O2Si | 详情 | 详情 | |
| (III) | 52564 | 4-(1-methylethyl)-3-[(4-nitrophenyl)sulfonyl]-1,3,2-oxazaborolidin-5-one | C11H13BN2O6S | 详情 | 详情 | |
| (IV) | 52565 | phenyl 5-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-hydroxy-2,2-dimethylpentanoate | C19H32O4Si | 详情 | 详情 | |
| (V) | 52566 | phenyl 3,5-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,2-dimethylpentanoate | C25H46O4Si2 | 详情 | 详情 | |
| (VI) | 40830 | (5S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-3-heptanone | C21H46O3Si2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XX)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5
该中间体在本合成路线中的序号：(I)The ketonic intermediate (VI) has been obtained as follows: The condensation of the 3-(tert-butyldimethylsilyloxy)propionaldehyde (I) with the silylated enol ether (II), catalyzed by the chiral boron reagent (III), gives the phenyl hydroxyester (IV), which is protected with Tbdms-Cl to provide the silyl ether (V). Finally, the Grignard reaction of (V) with Et-MgBr affords the target ketonic intermediate (VI).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 45546 | 3-[[tert-butyl(dimethyl)silyl]oxy]propanal | 570-24-1 | C9H20O2Si | 详情 | 详情 |
| (II) | 52563 | trimethyl{[2-methyl-1-(phenyloxy)-1-propenyl]oxy}silane; 2-methyl-1-(phenyloxy)-1-propenyl trimethylsilyl ether | C13H20O2Si | 详情 | 详情 | |
| (III) | 52564 | 4-(1-methylethyl)-3-[(4-nitrophenyl)sulfonyl]-1,3,2-oxazaborolidin-5-one | C11H13BN2O6S | 详情 | 详情 | |
| (IV) | 52565 | phenyl 5-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-hydroxy-2,2-dimethylpentanoate | C19H32O4Si | 详情 | 详情 | |
| (V) | 52566 | phenyl 3,5-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,2-dimethylpentanoate | C25H46O4Si2 | 详情 | 详情 | |
| (VI) | 40830 | (5S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-3-heptanone | C21H46O3Si2 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XXXIII)The condensation of 3-(tert-butyldimethylsilyloxy)propanal (XXXIII) with the chiral borane (XXXIV) by means of H2O2 and NaHCO3 gives the chiral alcohol (XXXV), which is oxidized with OsO4 and NaIO4 to yield the aldehyde (XXXVI). The Wittig condensation of (XXXVI) with phosphorane (XVI) affords the heptenoic ester (XXXVII), which is reduced with H2 over Pd/C to provide the saturated hydroxy ester (XXXVIII). The cyclization of (XXXVIII) by means of PPTS in refluxing dichloromethane gives the lactone (XXXIX), which by reaction with Cp2TiMe2 yields the methylene derivative (I).
| 【1】 Guzzupe, A.N.; et al.; Total synthesis of the epidermal growth factor inhibitor (-)-reveromycin B. J Org Chem 2001, 66, 7, 2382. |
| 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) | 41537 | tert-butyl(dimethyl)[2-[(2R,3S)-3-methyl-6-methylenetetrahydro-2H-pyran-2-yl]ethoxy]silane; tert-butyl(dimethyl)silyl 2-[(2R,3S)-3-methyl-6-methylenetetrahydro-2H-pyran-2-yl]ethyl ether | C15H30O2Si | 详情 | 详情 | |
| (XVI) | 14689 | Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate | 2605-67-6 | C21H19O2P | 详情 | 详情 |
| (XXXIII) | 45546 | 3-[[tert-butyl(dimethyl)silyl]oxy]propanal | 570-24-1 | C9H20O2Si | 详情 | 详情 |
| (XXXIV) | 50353 | (E)-2-butenyl[bis[(1R,2R,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane | C24H41B | 详情 | 详情 | |
| (XXXV) | 50354 | (3R,4S)-1-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-hexen-3-ol | C13H28O2Si | 详情 | 详情 | |
| (XXXVI) | 50355 | (2R,3R)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-2-methylpentanal | C12H26O3Si | 详情 | 详情 | |
| (XXXVII) | 50356 | methyl (E,4S,5R)-7-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4-methyl-2-heptenoate | C15H30O4Si | 详情 | 详情 | |
| (XXXVIII) | 50357 | methyl (4S,5R)-7-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4-methylheptanoate | C15H32O4Si | 详情 | 详情 | |
| (XXXIX) | 50358 | (5S,6R)-6-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-5-methyltetrahydro-2H-pyran-2-one | C14H28O3Si | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(XLV)The aldol condensation of 4-methoxy-alpha-methyl-cinnamaldehyde (XXXVIII) with the enol ether of 3-pentanone (XXXIX) gives the racemic aldol (rac)-(XL), which is submitted to an enantioselective retroaldol reaction catalyzed by antibody 38C2 yielding the chiral aldol (3R,4R)-(XLI). The reduction of the double bond of (XLI) with H2 over Rh/Al2O3 in THF affords the saturated hydroxyketone (XLII), which is treated with Tbdms-Cl and imidazole to provide the silyl ether (XLIII). The methylation of (XLIII) with methyl iodide and LDA in THF gives the isopropyl ketone (XLIV), which is condensed with aldehyde (XLV) by means of LDA in THF to yield the aldol (XLVI). The reaction of (XLVI) with Tbdms-Cl and imidazole affords the tris-silyl ether (XLVII), which is oxidized at the aromatic ring by means of RuCl3 and NaIO4 to provide the aldehyde (XLVIII).
| 【1】 Sinha, S.C.; Barbas, C.F. III; Lerner, R.A.; The antibody catalysis route to the total synthesis of epothilones. Proc Natl Acad Sci USA 1998, 95, 25, 14603. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (rac)-(XL) | 45542 | (rac)-(4R*,5R*,6E)-5-hydroxy-7-(4-methoxyphenyl)-4,6-dimethyl-6-hepten-3-one | 2592-19-0 | C16H22O3 | 详情 | 详情 |
| (3R, 4R)-(XLI) | 55588 | (4R,5R,6E)-5-hydroxy-7-(4-methoxyphenyl)-4,6-dimethyl-6-hepten-3-one | C16H22O3 | 详情 | 详情 | |
| (XXXVIII) | 45540 | (E)-3-(4-methoxyphenyl)-2-methyl-2-propenoic acid | C11H12O3 | 详情 | 详情 | |
| (XXXIX) | 45541 | (E)-1-ethyl-1-propenyl dibutylborinate | C13H27BO | 详情 | 详情 | |
| (XLII) | 45543 | (4R,5S,6S)-5-hydroxy-7-(4-methoxyphenyl)-4,6-dimethyl-3-heptanone | 71-44-3 | C16H24O3 | 详情 | 详情 |
| (XLIII) | 45544 | (4R,5S,6S)-5-[[tert-butyl(dimethyl)silyl]oxy]-7-(4-methoxyphenyl)-4,6-dimethyl-3-heptanone | C22H38O3Si | 详情 | 详情 | |
| (XLIV) | 45545 | (4R,5S,6S)-5-[[tert-butyl(dimethyl)silyl]oxy]-7-(4-methoxyphenyl)-2,4,6-trimethyl-3-heptanone | C23H40O3Si | 详情 | 详情 | |
| (XLV) | 45546 | 3-[[tert-butyl(dimethyl)silyl]oxy]propanal | 570-24-1 | C9H20O2Si | 详情 | 详情 |
| (XLVI) | 45547 | (5S,6R,9S)-9-hydroxy-5-[(1S)-2-(4-methoxyphenyl)-1-methylethyl]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disilapentadecan-7-one | 18063-02-0 | C32H60O5Si2 | 详情 | 详情 |
| (XLVII) | 45547 | (5S,6R,9S)-9-hydroxy-5-[(1S)-2-(4-methoxyphenyl)-1-methylethyl]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disilapentadecan-7-one | 18063-02-0 | C32H60O5Si2 | 详情 | 详情 |
| (XLVIII) | 45549 | (3S,4S,5R,8S)-4,8,10-tris[[tert-butyl(dimethyl)silyl]oxy]-3,5,7,7-tetramethyl-6-oxodecanal | C32H68O5Si3 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(VIII)The intermediate carboxylic acid (XVIII) has been obtained as follows: The aldol condensation of 4-methoxy-alpha-methyl-cinnamaldehyde (I) with the enol ether of 3-pentanone (II) gives the racemic aldol (rac)-(III), which is submitted to an enantioselective retroaldol reaction catalyzed by antibody 38C2, yielding the chiral aldol (3R,4R)-(IV). The reduction of the double bond of (IV) with H2 over Rh/Al2O3 in THF affords the saturated hydroxyketone (V), which is treated with Tbdms-Cl and imidazole to provide the silyl ether (VI). The methylation of (VI) with methyl iodide and LDA in THF gives the isopropyl ketone (VII), which is condensed with aldehyde (VIII) by means of LDA in THF to yield the aldol (IX). The reaction of (IX) with Tbdms-Cl and imidazole affords the tris-silyl ether (X), which is oxidized at the aromatic ring by means of RuCl3 and NaIO4 to provide the aldehyde (XI).
| 【1】 Sinha, S.C.; Barbas, C.F. III; Lerner, R.A.; The antibody catalysis route to the total synthesis of epothilones. Proc Natl Acad Sci USA 1998, 95, 25, 14603. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (rac)-(III) | 45542 | (rac)-(4R*,5R*,6E)-5-hydroxy-7-(4-methoxyphenyl)-4,6-dimethyl-6-hepten-3-one | 2592-19-0 | C16H22O3 | 详情 | 详情 |
| (3R, 4R)-(IV) | 55588 | (4R,5R,6E)-5-hydroxy-7-(4-methoxyphenyl)-4,6-dimethyl-6-hepten-3-one | C16H22O3 | 详情 | 详情 | |
| (I) | 45540 | (E)-3-(4-methoxyphenyl)-2-methyl-2-propenoic acid | C11H12O3 | 详情 | 详情 | |
| (II) | 45541 | (E)-1-ethyl-1-propenyl dibutylborinate | C13H27BO | 详情 | 详情 | |
| (V) | 45543 | (4R,5S,6S)-5-hydroxy-7-(4-methoxyphenyl)-4,6-dimethyl-3-heptanone | 71-44-3 | C16H24O3 | 详情 | 详情 |
| (VI) | 45544 | (4R,5S,6S)-5-[[tert-butyl(dimethyl)silyl]oxy]-7-(4-methoxyphenyl)-4,6-dimethyl-3-heptanone | C22H38O3Si | 详情 | 详情 | |
| (VII) | 45545 | (4R,5S,6S)-5-[[tert-butyl(dimethyl)silyl]oxy]-7-(4-methoxyphenyl)-2,4,6-trimethyl-3-heptanone | C23H40O3Si | 详情 | 详情 | |
| (VIII) | 45546 | 3-[[tert-butyl(dimethyl)silyl]oxy]propanal | 570-24-1 | C9H20O2Si | 详情 | 详情 |
| (IX) | 45547 | (5S,6R,9S)-9-hydroxy-5-[(1S)-2-(4-methoxyphenyl)-1-methylethyl]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disilapentadecan-7-one | 18063-02-0 | C32H60O5Si2 | 详情 | 详情 |
| (X) | 45548 | (5S,6R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-[(1S)-2-(4-methoxyphenyl)-1-methylethyl]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disilapentadecan-7-one | C38H74O5Si3 | 详情 | 详情 | |
| (XI) | 45549 | (3S,4S,5R,8S)-4,8,10-tris[[tert-butyl(dimethyl)silyl]oxy]-3,5,7,7-tetramethyl-6-oxodecanal | C32H68O5Si3 | 详情 | 详情 |