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【结 构 式】 
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【分子编号】44483 【品名】diethyl (E,4S,5R,6R)-4-(benzyloxy)-6-[[tert-butyl(dimethyl)silyl]oxy]-5,7,7-trimethyl-2-octenedioate 【CA登记号】 |
【 分 子 式 】C28H46O6Si 【 分 子 量 】506.75514 【元素组成】C 66.36% H 9.15% O 18.94% Si 5.54% |
合成路线1
该中间体在本合成路线中的序号：(XI)Synthesis of intermediate (XVI): The condensation of 3(S)-(phenyldimethylsilyl)-4(E)-hexenoic acid methyl ester (I) with 2-(tert-butyldimethylsilyloxy)acetaldehyde (II) by means of Tms-OBn, Tms-OTf and BF3/Et2O in dichloromethane gives the 3(E)-heptenoic ester (III), which is ozonolyzed with O3 and pyridine in methanol/dichloromethane to yield the aldehyde (IV). The condensation of (IV) with the silyl ketal (V) by means of TiCl4 in dichloromethane affords the partially protected trihydroxyester (VI), which is silylated with Tbdms-OTf and lutidine in dichloromethane to provide the fully protected ester (VII). Regioselective monodesilylation of (VII) by means of TBAF/HOAc in THF gives the primary alcohol (VIII), which is oxidized with oxalyl chloride to the corresponding aldehyde (IX). The condensation of (IX) with phosphorane (X) in refluxing benzene yields the octenedioic diester (XI), which is methylated with Me2CuLi and Tms-Cl in THF, affording the tetramethyl diester (XII). The two ester groups of (XII) were easily differentiated by a reduction with DIBAL in dichloromethane, providing the 8-hydroxyoctanal derivative (XIII), which was silylated with TBdms-Cl and imidazole in DMF to give the fully protected aldehyde (XIV). Finally, this compound was subjected to a Wittig olefination reaction with methyltriphenylphosphonium bromide (XV) and NaHMDS in THF to yield the desired intermediate (XVI).
| 【1】 Panek, J.S.; Zhu, B.; Total synthesis of apothilone A. Org Lett 2000, 2, 17, 2575. |
| 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) | 44474 | methyl (3S,4E)-3-[dimethyl(phenyl)silyl]-4-hexenoate | C15H22O2Si | 详情 | 详情 | |
| (II) | 44475 | 2-[[tert-butyl(diphenyl)silyl]oxy]acetaldehyde | C18H22O2Si | 详情 | 详情 | |
| (III) | 44476 | methyl (E,5S,6R)-6-(benzyloxy)-7-[[tert-butyl(diphenyl)silyl]oxy]-5-methyl-3-heptenoate | C32H40O4Si | 详情 | 详情 | |
| (IV) | 44477 | (2R,3R)-3-(benzyloxy)-4-[[tert-butyl(diphenyl)silyl]oxy]-2-methylbutanal | C28H34O3Si | 详情 | 详情 | |
| (V) | 44478 | 1-Ethoxy-2-methyl-1-trimethylsiloxypropene;1-Ethoxy-2-methyl-1-(trimethylsilyloxy)propene;1-Ethoxy-2-methyl-1-(trimethylsilyl)oxy-1-propene;1-ethoxy-2-methyl-1-propenyl trimethylsilyl ether; [(1-ethoxy-2-methyl-1-propenyl)oxy](trimethyl)silane ;dimethylketene ethyl trimethylsilyl acetal | 31469-16-6 | C9H20O2Si | 详情 | 详情 |
| (VI) | 44479 | ethyl (3R,4S,5R)-5-(benzyloxy)-6-[[tert-butyl(diphenyl)silyl]oxy]-3-hydroxy-2,2,4-trimethylhexanoate | C34H46O5Si | 详情 | 详情 | |
| (VII) | 44480 | ethyl (3R,4R,5R)-5-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-[[tert-butyl(diphenyl)silyl]oxy]-2,2,4-trimethylhexanoate | C40H60O5Si2 | 详情 | 详情 | |
| (VIII) | 44481 | ethyl (3R,4R,5R)-5-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-hydroxy-2,2,4-trimethylhexanoate | C24H42O5Si | 详情 | 详情 | |
| (IX) | 44482 | ethyl (3R,4R,5R)-5-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,2,4-trimethyl-6-oxohexanoate | C24H40O5Si | 详情 | 详情 | |
| (X) | 14182 | ethyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate; (Carbethoxymethylene)triphenylphosphorane | 1099-45-2 | C22H21O2P | 详情 | 详情 |
| (XI) | 44483 | diethyl (E,4S,5R,6R)-4-(benzyloxy)-6-[[tert-butyl(dimethyl)silyl]oxy]-5,7,7-trimethyl-2-octenedioate | C28H46O6Si | 详情 | 详情 | |
| (XII) | 44484 | diethyl (3R,4R,5S,6S)-5-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,2,4,6-tetramethyloctanedioate | C29H50O6Si | 详情 | 详情 | |
| (XIII) | 44485 | (3S,4S,5R,6R)-4-(benzyloxy)-6-[[tert-butyl(dimethyl)silyl]oxy]-8-hydroxy-3,5,7,7-tetramethyloctanal | C25H44O4Si | 详情 | 详情 | |
| (XIV) | 44486 | (3S,4S,5R,6R)-4-(benzyloxy)-6,8-bis[[tert-butyl(dimethyl)silyl]oxy]-3,5,7,7-tetramethyloctanal | C31H58O4Si2 | 详情 | 详情 | |
| (XV) | 30484 | Methyl(triphenyl)phosphonium bromide | 1779-49-3 | C19H18BrP | 详情 | 详情 |
| (XVI) | 44487 | (5R)-5-[(1R,2S,3S)-2-(benzyloxy)-1,3-dimethyl-5-hexenyl]-2,2,3,3,6,6,9,9,10,10-decamethyl-4,8-dioxa-3,9-disilaundecane; benzyl (1S,2S)-1-((1R,2R)-2,4-bis[[tert-butyl(dimethyl)silyl]oxy]-1,3,3-trimethylbutyl)-2-methyl-4-pentenyl ether | C32H60O3Si2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XI)Synthesis of intermediate (XVI): The condensation of 3(S)-(phenyldimethylsilyl)-4(E)-hexenoic acid methyl ester (I) with 2-(tert-butyldimethylsilyloxy)acetaldehyde (II) by means of Tms-OBn, Tms-OTf and BF3/Et2O in dichloromethane gives the 3(E)-heptenoic ester (III), which is ozonolyzed with O3 and pyridine in methanol/dichloromethane to yield the aldehyde (IV). The condensation of (IV) with the silyl ketal (V) by means of TiCl4 in dichloromethane affords the partially protected trihydroxyester (VI), which is silylated with Tbdms-OTf and lutidine in dichloromethane to provide the fully protected ester (VII). Regioselective monodesilylation of (VII) by means of TBAF/AcOH in THF gives the primary alcohol (VIII), which is oxidized with oxalyl chloride to the corresponding aldehyde (IX). The condensation of (IX) with phosphorane (X) in refluxing benzene yields the octenedioic diester (XI), which is methylated with Me2CuLi and Tms-Cl in THF, affording the tetramethyl diester (XII). The two ester groups of (XII) were easily differentiated by a reduction with DIBAL in dichloromethane, providing the 8-hydroxyoctanal derivative (XIII), which was silylated with TBdms-Cl and imidazole in DMF to give the fully protected aldehyde (XIV). Finally, this compound was subjected to a Wittig olefination reaction with methyltriphenylphosphonium bromide (XV) and NaHMDS in THF to yield the desired intermediate (XVI).
| 【1】 Panek, J.S.; Zhu, B.; Total synthesis of apothilone A. Org Lett 2000, 2, 17, 2575. |
| 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) | 44474 | methyl (3S,4E)-3-[dimethyl(phenyl)silyl]-4-hexenoate | C15H22O2Si | 详情 | 详情 | |
| (II) | 44475 | 2-[[tert-butyl(diphenyl)silyl]oxy]acetaldehyde | C18H22O2Si | 详情 | 详情 | |
| (III) | 44476 | methyl (E,5S,6R)-6-(benzyloxy)-7-[[tert-butyl(diphenyl)silyl]oxy]-5-methyl-3-heptenoate | C32H40O4Si | 详情 | 详情 | |
| (IV) | 44477 | (2R,3R)-3-(benzyloxy)-4-[[tert-butyl(diphenyl)silyl]oxy]-2-methylbutanal | C28H34O3Si | 详情 | 详情 | |
| (V) | 44478 | 1-Ethoxy-2-methyl-1-trimethylsiloxypropene;1-Ethoxy-2-methyl-1-(trimethylsilyloxy)propene;1-Ethoxy-2-methyl-1-(trimethylsilyl)oxy-1-propene;1-ethoxy-2-methyl-1-propenyl trimethylsilyl ether; [(1-ethoxy-2-methyl-1-propenyl)oxy](trimethyl)silane ;dimethylketene ethyl trimethylsilyl acetal | 31469-16-6 | C9H20O2Si | 详情 | 详情 |
| (VI) | 44479 | ethyl (3R,4S,5R)-5-(benzyloxy)-6-[[tert-butyl(diphenyl)silyl]oxy]-3-hydroxy-2,2,4-trimethylhexanoate | C34H46O5Si | 详情 | 详情 | |
| (VII) | 44480 | ethyl (3R,4R,5R)-5-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-[[tert-butyl(diphenyl)silyl]oxy]-2,2,4-trimethylhexanoate | C40H60O5Si2 | 详情 | 详情 | |
| (VIII) | 44481 | ethyl (3R,4R,5R)-5-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-6-hydroxy-2,2,4-trimethylhexanoate | C24H42O5Si | 详情 | 详情 | |
| (IX) | 44482 | ethyl (3R,4R,5R)-5-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,2,4-trimethyl-6-oxohexanoate | C24H40O5Si | 详情 | 详情 | |
| (X) | 14182 | ethyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate; (Carbethoxymethylene)triphenylphosphorane | 1099-45-2 | C22H21O2P | 详情 | 详情 |
| (XI) | 44483 | diethyl (E,4S,5R,6R)-4-(benzyloxy)-6-[[tert-butyl(dimethyl)silyl]oxy]-5,7,7-trimethyl-2-octenedioate | C28H46O6Si | 详情 | 详情 | |
| (XII) | 44484 | diethyl (3R,4R,5S,6S)-5-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,2,4,6-tetramethyloctanedioate | C29H50O6Si | 详情 | 详情 | |
| (XIII) | 44485 | (3S,4S,5R,6R)-4-(benzyloxy)-6-[[tert-butyl(dimethyl)silyl]oxy]-8-hydroxy-3,5,7,7-tetramethyloctanal | C25H44O4Si | 详情 | 详情 | |
| (XIV) | 44486 | (3S,4S,5R,6R)-4-(benzyloxy)-6,8-bis[[tert-butyl(dimethyl)silyl]oxy]-3,5,7,7-tetramethyloctanal | C31H58O4Si2 | 详情 | 详情 | |
| (XV) | 30484 | Methyl(triphenyl)phosphonium bromide | 1779-49-3 | C19H18BrP | 详情 | 详情 |
| (XVI) | 44487 | (5R)-5-[(1R,2S,3S)-2-(benzyloxy)-1,3-dimethyl-5-hexenyl]-2,2,3,3,6,6,9,9,10,10-decamethyl-4,8-dioxa-3,9-disilaundecane; benzyl (1S,2S)-1-((1R,2R)-2,4-bis[[tert-butyl(dimethyl)silyl]oxy]-1,3,3-trimethylbutyl)-2-methyl-4-pentenyl ether | C32H60O3Si2 | 详情 | 详情 |