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【结 构 式】 
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【分子编号】45549 【品名】(3S,4S,5R,8S)-4,8,10-tris[[tert-butyl(dimethyl)silyl]oxy]-3,5,7,7-tetramethyl-6-oxodecanal 【CA登记号】 |
【 分 子 式 】C32H68O5Si3 【 分 子 量 】617.14542 【元素组成】C 62.28% H 11.11% O 12.96% Si 13.65% |
合成路线1
该中间体在本合成路线中的序号：(XI)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：(XI)The condensation of (XI) with phosphonate (XII) by means of NaH in THF furnishes the unsaturated ester (XIII). The reduction of the double bond of (XIII) with H2 over Rh/Al2O3, followed by reduction of the ester group with DIBAL and oxidation of the resulting alcohol with DMP, gives rise to the aldehyde (XIV). The Wittig condensation of (XIV) with phosphonium salt (XV) by means of BuLi in THF yields the terminal olefin (XVI), which is selectively desilylated with Ts-OH to afford the primary alcohol (XVII). Finally, this compound is oxidized to the target carboxylic acid intermediate (XVIII) with DMP and NaClO2 in dichloromethane/THF.
| 【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 |
|---|---|---|---|---|---|---|
| (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 | |
| (XII) | 35909 | ethyl 3-(diethoxyphosphoryl)propanoate | 3699-67-0 | C9H19O5P | 详情 | 详情 |
| (XIII) | 45550 | ethyl (E,5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxo-2-dodecenoate | 2463-77-6 | C36H74O6Si3 | 详情 | 详情 |
| (XIV) | 45551 | (5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxododecanal | 94-59-7 | C34H72O5Si3 | 详情 | 详情 |
| (XV) | 13484 | Methyl(triphenyl)phosphonium iodide; Methyltriphenylphosphonium iodide | 2065-66-9 | C19H18IP | 详情 | 详情 |
| (XVI) | 44436 | (5S,6R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-5-hexenyl]-4,12-dioxa-3,13-disilapentadecan-7-one | C35H74O4Si3 | 详情 | 详情 | |
| (XVII) | 44437 | (5S,8R,9S)-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,11,11,12,12-undecamethyl-9-[(1S)-1-methyl-5-hexenyl]-4,10-dioxa-3,11-disilatridecan-7-one | C29H60O4Si2 | 详情 | 详情 | |
| (XVIII) | 44438 | (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid | C29H58O5Si2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XLVIII)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4
该中间体在本合成路线中的序号：(XLVIII)The condensation of (XLVIII) with phosphonate (XLIX) by means of NaH in THF furnishes the unsaturated ester (L). The reduction of the double bond of (L) with H2 over Rh/Al2O3, followed by reduction of the ester group with DIBAL and oxidation of the resulting alcohol with DMP, gives rise to the aldehyde (LI). The Wittig condensation of (LI) with phosphonium salt (LII) by means of BuLi in THF yields the terminal olefin (LIII), which is selectively desilylated with TsOH to afford the primary alcohol (LIV). Finally, this compound is oxidized to the target carboxylic acid intermediate (XII) with DMP and NaClO2 in dichloromethane/THF.
| 【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 |
|---|---|---|---|---|---|---|
| (IL) | 35909 | ethyl 3-(diethoxyphosphoryl)propanoate | 3699-67-0 | C9H19O5P | 详情 | 详情 |
| (XII) | 44438 | (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid | C29H58O5Si2 | 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 | |
| (L) | 45550 | ethyl (E,5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxo-2-dodecenoate | 2463-77-6 | C36H74O6Si3 | 详情 | 详情 |
| (LI) | 45551 | (5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxododecanal | 94-59-7 | C34H72O5Si3 | 详情 | 详情 |
| (LII) | 13484 | Methyl(triphenyl)phosphonium iodide; Methyltriphenylphosphonium iodide | 2065-66-9 | C19H18IP | 详情 | 详情 |
| (LIII) | 44436 | (5S,6R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-5-hexenyl]-4,12-dioxa-3,13-disilapentadecan-7-one | C35H74O4Si3 | 详情 | 详情 | |
| (LIV) | 44437 | (5S,8R,9S)-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,11,11,12,12-undecamethyl-9-[(1S)-1-methyl-5-hexenyl]-4,10-dioxa-3,11-disilatridecan-7-one | C29H60O4Si2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(XI)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6
该中间体在本合成路线中的序号：(XI)The condensation of (XI) with phosphonate (XII) by means of NaH in THF furnishes the unsaturated ester (XIII). The reduction of the double bond of (XIII) with H2 over Rh/Al2O3, followed by reduction of the ester group with DIBAL and oxidation of the resulting alcohol with DMP, gives rise to the aldehyde (XIV). The Wittig condensation of (XIV) with phosphonium salt (XV) by means of BuLi in THF yields the terminal olefin (XVI), which is selectively desilylated with Ts-OH to afford the primary alcohol (XVII). Finally, this compound is oxidized to the target carboxylic acid intermediate (XVIII) with DMP and NaClO2 in dichloromethane/THF.
| 【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 |
|---|---|---|---|---|---|---|
| (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 | |
| (XII) | 35909 | ethyl 3-(diethoxyphosphoryl)propanoate | 3699-67-0 | C9H19O5P | 详情 | 详情 |
| (XIII) | 45550 | ethyl (E,5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxo-2-dodecenoate | 2463-77-6 | C36H74O6Si3 | 详情 | 详情 |
| (XIV) | 45551 | (5S,6S,7R,10S)-6,10,12-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7,9,9-tetramethyl-8-oxododecanal | 94-59-7 | C34H72O5Si3 | 详情 | 详情 |
| (XV) | 13484 | Methyl(triphenyl)phosphonium iodide; Methyltriphenylphosphonium iodide | 2065-66-9 | C19H18IP | 详情 | 详情 |
| (XVI) | 44436 | (5S,6R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-5-hexenyl]-4,12-dioxa-3,13-disilapentadecan-7-one | C35H74O4Si3 | 详情 | 详情 | |
| (XVII) | 44437 | (5S,8R,9S)-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,11,11,12,12-undecamethyl-9-[(1S)-1-methyl-5-hexenyl]-4,10-dioxa-3,11-disilatridecan-7-one | C29H60O4Si2 | 详情 | 详情 | |
| (XVIII) | 44438 | (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid | C29H58O5Si2 | 详情 | 详情 |