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【结 构 式】 
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【分子编号】42716 【品名】(5S,6Z,8S,9S)-9-[(1S,2Z)-4-bromo-1,3-dimethyl-2-butenyl]-5-[[(2S,3S,4S,5R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]methyl]-2,2,3,3,8,11,11,12,12-nonamethyl-4,10-dioxa-3,11-disila-6-tridecene; (2S,3S,4S,5R,6S)-2-((2S,3Z,5S,6S,7S,8Z)-10-bromo-2,6-bis[[tert-butyl(dimethyl)silyl]oxy]-5,7,9-trimethyl-3,8-decadienyl)-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-4-yl tert-butyl(dimethyl)silyl ether 【CA登记号】n/a |
【 分 子 式 】C44H81BrO4SSi3 【 分 子 量 】870.35124 【元素组成】C 60.72% H 9.38% Br 9.18% O 7.35% S 3.68% Si 9.68% |
合成路线1
该中间体在本合成路线中的序号：(XXXIII)The intermediate (XXXIII) has been obtained as follows: The silylation of the OH group of (2S,3R,4S)-2,4-dimethyl-1-(tert-butyldimethylsilyloxy)-5-hexen-3-ol (XVII) with Tbdms-OTf gives the bis-silyl ether (XVIII), which is ozonolyzed with O3 to yield the aldehyde (XIX). The condensation of (XIX) with the phosphonate (XX) by means of KHMDS affords the methyl heptenoate (XXI), which is reduced with LiAlH4 to the carbinol (XXII). The esterification of (XXII) with pivaloyl chloride and pyridine affords the pivaloyl ester (XXIII), which is selectively desilylated with HF and pyridine to provide the primary alcohol (XXIV). The Swern oxidation of (XXIV) gives the aldehyde (XXV), which is condensed with the phosphonate (XXVI) to yield the terminal acetylene derivative (XXVII). Iodination of (XXVII) with I2 and morpholine affords the iodoacetylene (XXVIII), which is condensed with the already reported acetaldehyde intermediate (XVI) by means of NiCl2/CuCl2 to provide the acetylenic alcohol (XXIX). The reduction of the triple bond of (XXIX) with H2 over Pd/C gives the corresponding allyl alcohol derivative (XXX), which is silylated with Tbdms-OTf to the trisilylated compound (XXXI). Elimination of the pivaloyl protecting group of (XXXI) by means of DIBAL yields the primary alcohol (XXXII), which is treated first with MsCl and TEA and then with LiBr to furnish the target bromoderivative intermediate (XXXIII).
| 【1】 Hung, D.T.; et al.; Syntheses of discodermolides useful for investigating microtubule binding and stabilization. J Am Chem Soc 1996, 118, 45, 11054. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVI) | 42700 | 2-[(2S,3S,4S,5R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]acetaldehyde | C21H34O3SSi | 详情 | 详情 | |
| (XVII) | 42701 | (2S,3R,4S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2,4-dimethyl-5-hexen-3-ol | C14H30O2Si | 详情 | 详情 | |
| (XVIII) | 42381 | (5S,6R)-2,2,3,3,6,9,9,10,10-nonamethyl-5-[(1R)-1-methyl-2-propenyl]-4,8-dioxa-3,9-disilaundecane; tert-butyl(dimethyl)silyl (2R,3S,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,4-dimethyl-5-hexenyl ether | C20H44O2Si2 | 详情 | 详情 | |
| (XIX) | 42702 | (2R,3S,4S)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2,4-dimethylpentanal | C19H42O3Si2 | 详情 | 详情 | |
| (XX) | 42703 | methyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]propanoate | C8H11F6O5P | 详情 | 详情 | |
| (XXI) | 42704 | methyl (Z,4S,5R,6S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-2,4,6-trimethyl-2-heptenoate | C23H48O4Si2 | 详情 | 详情 | |
| (XXII) | 42705 | (Z,4S,5R,6S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-2,4,6-trimethyl-2-hepten-1-ol | C22H48O3Si2 | 详情 | 详情 | |
| (XXIII) | 42706 | (Z,4S,5R,6S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-2,4,6-trimethyl-2-heptenyl pivalate | C27H56O4Si2 | 详情 | 详情 | |
| (XXIV) | 42707 | (Z,4S,5R,6S)-5-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-2,4,6-trimethyl-2-heptenyl pivalate | C21H42O4Si | 详情 | 详情 | |
| (XXV) | 42708 | (Z,4S,5R,6R)-5-[[tert-butyl(dimethyl)silyl]oxy]-2,4,6-trimethyl-7-oxo-2-heptenyl pivalate | C21H40O4Si | 详情 | 详情 | |
| (XXVI) | 42709 | Diazomethylphoshonic acid dimethyl ester | 27491-70-9 | C3H7N2O3P | 详情 | 详情 |
| (XXVII) | 42710 | (Z,4S,5R,6S)-5-[[tert-butyl(dimethyl)silyl]oxy]-2,4,6-trimethyl-2-octen-7-ynyl pivalate | C22H40O3Si | 详情 | 详情 | |
| (XXVIII) | 42711 | (Z,4S,5R,6S)-5-[[tert-butyl(dimethyl)silyl]oxy]-8-iodo-2,4,6-trimethyl-2-octen-7-ynyl pivalate | C22H39IO3Si | 详情 | 详情 | |
| (XXIX) | 42712 | (Z,4S,5R,6S,9S)-5-[[tert-butyl(dimethyl)silyl]oxy]-10-[(2S,3S,4S,5R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]-9-hydroxy-2,4,6-trimethyl-2-decen-7-ynyl 2,2-dimethylpropanoate | C43H74O6SSi2 | 详情 | 详情 | |
| (XXX) | 42713 | (2Z,4S,5S,6S,7Z,9S)-5-[[tert-butyl(dimethyl)silyl]oxy]-10-[(2S,3S,4S,5R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]-9-hydroxy-2,4,6-trimethyl-2,7-decadienyl 2,2-dimethylpropanoate | C43H76O6SSi2 | 详情 | 详情 | |
| (XXXI) | 42714 | (2Z,4S,5S,6S,7Z,9S)-5,9-bis[[tert-butyl(dimethyl)silyl]oxy]-10-[(2S,3S,4S,5R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]-2,4,6-trimethyl-2,7-decadienyl 2,2-dimethylpropanoate | n/a | C49H90O6SSi3 | 详情 | 详情 |
| (XXXII) | 42715 | (2Z,4S,5S,6S,7Z,9S)-5,9-bis[[tert-butyl(dimethyl)silyl]oxy]-10-[(2S,3S,4S,5R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]-2,4,6-trimethyl-2,7-decadien-1-ol | n/a | C44H82O5SSi3 | 详情 | 详情 |
| (XXXIII) | 42716 | (5S,6Z,8S,9S)-9-[(1S,2Z)-4-bromo-1,3-dimethyl-2-butenyl]-5-[[(2S,3S,4S,5R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]methyl]-2,2,3,3,8,11,11,12,12-nonamethyl-4,10-dioxa-3,11-disila-6-tridecene; (2S,3S,4S,5R,6S)-2-((2S,3Z,5S,6S,7S,8Z)-10-bromo-2,6-bis[[tert-butyl(dimethyl)silyl]oxy]-5,7,9-trimethyl-3,8-decadienyl)-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-4-yl tert-butyl(dimethyl)silyl ether | n/a | C44H81BrO4SSi3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXIII)The target compound has been obtained as follows: The condensation of bromo derivative intermediate (XXXIII) with the ketone intermediate (XLIII) by means of LDA gives the adduct (L), which is methylated with methyl iodide and (Tbdps)2N-Li to yield the pentamethyl compound (LI). The desulfuration of (LI) by reaction with HgCl2 followed by oxidation with Jones reagent affords the tetrahydroyranone derivative (LII), which is debenzylated by means of DDQ to furnish the secondary alcohol (LIII). The reaction of (LIII) with trichloroacetyl isocyanate gives the carbamate (LIV), which is reduced with LiAlH(OBu)3I, yielding the secondary alcohol (LV). Finally, this compound is desilylated by treatment with HCl in methanol.
| 【1】 Hung, D.T.; et al.; Syntheses of discodermolides useful for investigating microtubule binding and stabilization. J Am Chem Soc 1996, 118, 45, 11054. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIII) | 42716 | (5S,6Z,8S,9S)-9-[(1S,2Z)-4-bromo-1,3-dimethyl-2-butenyl]-5-[[(2S,3S,4S,5R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]methyl]-2,2,3,3,8,11,11,12,12-nonamethyl-4,10-dioxa-3,11-disila-6-tridecene; (2S,3S,4S,5R,6S)-2-((2S,3Z,5S,6S,7S,8Z)-10-bromo-2,6-bis[[tert-butyl(dimethyl)silyl]oxy]-5,7,9-trimethyl-3,8-decadienyl)-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-4-yl tert-butyl(dimethyl)silyl ether | n/a | C44H81BrO4SSi3 | 详情 | 详情 |
| (XLIII) | 42722 | (3R,4S,5S,6Z)-4-[(4-methoxybenzyl)oxy]-3,5-dimethyl-6,8-nonadien-2-one | C19H26O3 | 详情 | 详情 | |
| (L) | 42729 | (3Z,5S,6S,7R,11Z,13S,14S,15S,16Z,18S)-14,18-bis[[tert-butyl(dimethyl)silyl]oxy]-19-[(2S,3S,4S,5R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]-6-[(4-methoxybenzyl)oxy]-5,7,11,13,15-pentamethyl-1,3,11 | C63H106O7SSi3 | 详情 | 详情 | |
| (LI) | 42730 | (3Z,5S,6S,7R,9S,11Z,13S,14S,15S,16Z,18S)-14,18-bis[[tert-butyl(dimethyl)silyl]oxy]-19-[(2S,3S,4S,5R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]-6-[(4-methoxybenzyl)oxy]-5,7,9,11,13,15-hexamethyl-1, | C64H108O7SSi3 | 详情 | 详情 | |
| (LII) | 42731 | (3R,4S,5S,6S)-6-[(2S,3Z,5S,6S,7S,8Z,11S,13R,14S,15S,16Z)-2,6-bis[[tert-butyl(dimethyl)silyl]oxy]-14-[(4-methoxybenzyl)oxy]-5,7,9,11,13,15-hexamethyl-12-oxo-3,8,16,18-nonadecatetraenyl]-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyltetrahydro-2H-pyr | C58H102O8Si3 | 详情 | 详情 | |
| (LIII) | 42732 | (3R,4S,5S,6S)-6-((2S,3Z,5S,6S,7S,8Z,11S,13R,14S,15S,16Z)-2,6-bis[[tert-butyl(dimethyl)silyl]oxy]-14-hydroxy-5,7,9,11,13,15-hexamethyl-12-oxo-3,8,16,18-nonadecatetraenyl)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyltetrahydro-2H-pyran-2-one | C50H94O7Si3 | 详情 | 详情 | |
| (LIV) | 42733 | (1S,2R,4S,6Z,8S,9S,10S,11Z,13S)-9,13-bis[[tert-butyl(dimethyl)silyl]oxy]-14-((2S,3S,4S,5R)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-oxotetrahydro-2H-pyran-2-yl)-2,4,6,8,10-pentamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-3-oxo-6,11-tetradec | C51H95NO8Si3 | 详情 | 详情 | |
| (LV) | 42734 | (1S,2S,3R,4S,6Z,8S,9S,10S,11Z,13S)-9,13-bis[[tert-butyl(dimethyl)silyl]oxy]-14-((2S,3S,4S,5R)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-oxotetrahydro-2H-pyran-2-yl)-3-hydroxy-2,4,6,8,10-pentamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-6,11-t | C51H97NO8Si3 | 详情 | 详情 |