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【结 构 式】 
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【分子编号】42668 【品名】tert-butyl(dimethyl)silyl (1R,2S,3Z)-4-iodo-1-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-2-methyl-3-pentenyl ether; tert-butyl[((1R,2S,3Z)-4-iodo-1-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-2-methyl-3-pentenyl)oxy]dimethylsilane 【CA登记号】 |
【 分 子 式 】C23H39IO3Si 【 分 子 量 】518.55083 【元素组成】C 53.27% H 7.58% I 24.47% O 9.26% Si 5.42% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The intermediate (XVIII) has been obtained as follows: The silylation of the intermediate methoxyamide (VII) with Tbdms-OTf gives the silylated methoxyamide (XVI), which is reduced with DIBAL yielding the aldehyde (XVII). Finally, this compound is condensed with ethyltriphenylphosphonium iodide and BuLi and treated with I2 and NaHMDS to afford the intermediate iodo derivative (XVIII). The intermediate (XXV) has been obtained as follows: The hydrogenolysis of intermediate (XVI) with H2 over Pd/C gives the primary alcohol (XIX), which is oxidized with SO3 and pyridine, yielding the aldehyde (XX). The condensation of (XX) with the silylated enol ether (XXI) by means of TiCl4 and TFA affords the lactone (XXII), which is reduced with K-Selectride to provide the chiral alcohol (XXIII). The silylation of (XXIII) with Tbdms-Cl and imidazole gives the silyl ether (XXIV), which is finally ozonolyzed with O3 and PPh3 to yield the target intermediate aldehyde (XXV).
| 【1】 Smith, A.B. III; et al.; Gram-scale synthesis of (+)-discodermolide. Org Lett 1999, 1, 11, 1823. |
| 【2】 Smith, A.B. III; et al.; Evolution of a gram-scale synthesis of (+)-discodermolide. J Am Chem Soc 2000, 122, 36, 8654. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 42659 | (2R,3S,4S)-3-hydroxy-N-methoxy-5-[(4-methoxybenzyl)oxy]-N,2,4-trimethylpentanamide | C17H27NO5 | 详情 | 详情 | |
| (XVI) | 42666 | (2R,3S,4S)-3-[[tert-butyl(dimethyl)silyl]oxy]-N-methoxy-5-[(4-methoxybenzyl)oxy]-N,2,4-trimethylpentanamide | C23H41NO5Si | 详情 | 详情 | |
| (XVII) | 42667 | (2R,3S,4S)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanal | C21H36O4Si | 详情 | 详情 | |
| (XVIII) | 42668 | tert-butyl(dimethyl)silyl (1R,2S,3Z)-4-iodo-1-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-2-methyl-3-pentenyl ether; tert-butyl[((1R,2S,3Z)-4-iodo-1-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-2-methyl-3-pentenyl)oxy]dimethylsilane | C23H39IO3Si | 详情 | 详情 | |
| (XIX) | 42669 | (2R,3S,4S)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-N-methoxy-N,2,4-trimethylpentanamide | C15H33NO4Si | 详情 | 详情 | |
| (XX) | 42670 | (2R,3S,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-N-methoxy-N,2,4-trimethyl-5-oxopentanamide | C15H31NO4Si | 详情 | 详情 | |
| (XXI) | 42671 | 3-methyl-1-methylene-2-butenyl trimethylsilyl ether; trimethyl[(3-methyl-1-methylene-2-butenyl)oxy]silane | C9H18OSi | 详情 | 详情 | |
| (XXII) | 42672 | (3R,4S,5R,6S)-4-methoxy-3,5-dimethyl-6-(4-methyl-2-oxo-3-pentenyl)tetrahydro-2H-pyran-2-one | C14H22O4 | 详情 | 详情 | |
| (XXIII) | 42673 | (3R,4S,5R,6S)-6-[(2S)-2-hydroxy-4-methyl-3-pentenyl]-4-methoxy-3,5-dimethyltetrahydro-2H-pyran-2-one | C14H24O4 | 详情 | 详情 | |
| (XXIV) | 42674 | (3R,4S,5R,6S)-6-((2S)-2-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-3-pentenyl)-4-methoxy-3,5-dimethyltetrahydro-2H-pyran-2-one | C20H38O4Si | 详情 | 详情 | |
| (XXV) | 42675 | (2S)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-[(2S,3R,4S,5R)-4-methoxy-3,5-dimethyl-6-oxotetrahydro-2H-pyran-2-yl]propanal | C17H32O5Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVIII)The target compound has been obtained as follows: The reaction of intermediate iodo derivative (XV) with ZnCl2 and BuLi gives the organozinc compound (XXVI), which is condensed with intermediate iodo derivative (XVIII) by means of Pd(PPh3)4, yielding the adduct (XXVII). The selective deprotection of the Pmb group of (XXVII) with DDQ, followed by reprotection with Tr-Cl, affords the suitably protected adduct (XXVIII). Cleaving of the cyclic ketal group of (XXVIII) with DIBAL provides the primary alcohol (XXIX), which is oxidized with DMP, giving the aldehyde (XXX). The condensation of (XXX) with the titanium derivative (XXXI) yields the adduct (XXXII), which is selectively deprotected at the trityl group with chloro-catecholborane to afford the primary alcohol (XXXIII). The reaction of (XXXIII) with PPh3 , I2 and DIEA furnishes the phosphonium iodide (XXXIV).
| 【1】 Smith, A.B. III; et al.; Evolution of a gram-scale synthesis of (+)-discodermolide. J Am Chem Soc 2000, 122, 36, 8654. |
| 【2】 Smith, A.B. III; et al.; Gram-scale synthesis of (+)-discodermolide. Org Lett 1999, 1, 11, 1823. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 42665 | tert-butyl(dimethyl)silyl (1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl ether; tert-butyl[((1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl)oxy]dimethylsilane | C24H41IO4Si | 详情 | 详情 | |
| (XVIII) | 42668 | tert-butyl(dimethyl)silyl (1R,2S,3Z)-4-iodo-1-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-2-methyl-3-pentenyl ether; tert-butyl[((1R,2S,3Z)-4-iodo-1-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-2-methyl-3-pentenyl)oxy]dimethylsilane | C23H39IO3Si | 详情 | 详情 | |
| (XXVI) | 42676 | tert-butyl[(2R,3S,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-methylpentyl]zinc | C28H50O4SiZn | 详情 | 详情 | |
| (XXVII) | 42677 | (5R,6S,7Z,10S,11R)-5-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-11-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2,2,3,3,6,8,10,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disila-7-pentadecene; 4-((4S,5S)-4-[(1R,2R,3S,5Z,7S,8R,9S)-2,8-bis[[tert-butyl(dimethyl)silyl]oxy]-10-[(4-methoxybenzyl)oxy]-1,3,5,7,9-pentamethyl-5-decenyl]-5-methyl-1,3-dioxan-2-yl)phenyl methyl ether | C47H80O7Si2 | 详情 | 详情 | |
| (XXVIII) | 42678 | (5R,6S,7Z,10S,11R)-11-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2,2,3,3,6,8,10,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-2-(trityloxy)ethyl]-4,12-dioxa-3,13-disila-7-pentadecene; (2S,3R,4S,5Z,8S,9R,10R)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-10-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2,4,6,8-tetramethyl-5-undecenyl trityl ether | C58H86O6Si2 | 详情 | 详情 | |
| (XXIX) | 42679 | (2S,3S,4R,5R,6S,8Z,10S,11R,12S)-5,11-bis[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-13-(trityloxy)-8-tridecen-1-ol | C58H88O6Si2 | 详情 | 详情 | |
| (XXX) | 42680 | (2R,3R,4R,5R,6S,8Z,10S,11R,12S)-5,11-bis[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-13-(trityloxy)-8-tridecenal | C58H86O6Si2 | 详情 | 详情 | |
| (XXXI) | 42681 | C39H34LiO4PTi | 详情 | 详情 | ||
| (XXXII) | 42682 | (2S,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrienyl trityl ether; (5R,6S,7Z,10S,11R)-11-[(1R,2S,3S,4Z)-2-[(4-methoxybenzyl)oxy]-1,3-dimethyl-4,6-heptadienyl]-2,2,3,3,6,8,10,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-2-(trityloxy)ethyl]-4,12-dioxa-3,13-disila-7-pentadecene | C61H90O5Si2 | 详情 | 详情 | |
| (XXXIII) | 42683 | (2S,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrien-1-ol | C42H76O5Si2 | 详情 | 详情 | |
| (XXXIV) | 42684 | [(2R,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrienyl](triphenyl)phosphonium iodide | C60H90IO4PSi2 | 详情 | 详情 |