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【结 构 式】 
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【分子编号】42722 【品名】(3R,4S,5S,6Z)-4-[(4-methoxybenzyl)oxy]-3,5-dimethyl-6,8-nonadien-2-one 【CA登记号】 |
【 分 子 式 】C19H26O3 【 分 子 量 】302.41364 【元素组成】C 75.46% H 8.67% O 15.87% |
合成路线1
该中间体在本合成路线中的序号：(XLIII)The intermediate (XLIII) has been obtained in two related ways: 1) The protection of (2S,3S,4S)-2,4-dimethyl-1-(tert-butyldimethylsilyloxy)-5-hexen-3-ol (I) with p-methoxybenzyl bromide and NaH gives the benzyl ether (XXXIV) which is ozonolyzed with O3, yielding the aldehyde (XXXV), which is condensed with the phosphonium salt (XXXVI) by means of KHMDS to afford the iodovinyl derivative (XXXVII). The homologation of (XXXVII) with vinylzinc bromide (XXXVIII) provides the octadiene derivative (XXXIX), which is desilylated with TFA, furnishing the primary alcohol (XL). The oxidation of (XL) with DMP gives the aldehyde (XLI), which is treated with CH3-MgBr, yielding the secondary alcohol (XLII). Finally, this alcohol is oxidized with DMP to the target intermediate ketone (XLIII). 2) The protection of (2S,3R,4S)-2,4-dimethyl-1-(tert-butyldimethylsilyloxy)-5-hexen-3-ol (XVII) with p-methoxybenzyl bromide and NaH gives the benzyl ether (XLIV), which is ozonolyzed with O3, yielding the aldehyde (XLV). The reaction of (XLV) with CH3-MgBr affords the secondary alcohol (XLVI), which is desilylated with TFA.
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 42608 | [(1R,3S,4S)-4-aminospiro[2.2]pent-1-yl]methanol | C6H11NO | 详情 | 详情 | |
| (XXXIV) | 42717 | tert-butyl([(2S,3S,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl]oxy)dimethylsilane; tert-butyl(dimethyl)silyl (2S,3S,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl ether | n/a | C22H38O3Si | 详情 | 详情 |
| (XXXV) | 42628 | (2R,3R,4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanal | C21H36O4Si | 详情 | 详情 | |
| (XXXVI) | 42718 | (iodomethyl)(triphenyl)phosphonium iodide | n/a | C19H17I2P | 详情 | 详情 |
| (XXXVII) | 42719 | tert-butyl([(2S,3S,4S,5Z)-6-iodo-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl]oxy)dimethylsilane; tert-butyl(dimethyl)silyl (2S,3S,4S,5Z)-6-iodo-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl ether | n/a | C22H37IO3Si | 详情 | 详情 |
| (XXXVIII) | 42720 | bromo(vinyl)zinc | n/a | C2H3BrZn | 详情 | 详情 |
| (XXXIX) | 42630 | tert-butyl([(2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienyl]oxy)dimethylsilane; tert-butyl(dimethyl)silyl (2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienyl ether | C24H40O3Si | 详情 | 详情 | |
| (XL) | 42631 | (2S,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadien-1-ol | C18H26O3 | 详情 | 详情 | |
| (XLI) | 42632 | (2R,3S,4S,5Z)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5,7-octadienal | C18H24O3 | 详情 | 详情 | |
| (XLII) | 42721 | (3S,4S,5S,6Z)-4-[(4-methoxybenzyl)oxy]-3,5-dimethyl-6,8-nonadien-2-ol | C19H28O3 | 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 |
合成路线2
该中间体在本合成路线中的序号：(XLIII)The diol (XLVII) has been obtained as follows: The Swern oxidation of the OH groups of (XLVII) gives the 5-oxohexanal derivative (XLVIII), which is condensed with the phosphonium salt (XXXVI) to yield the iodovinyl derivative (XLIX). Finally, this compound is homologated with vinylzinc bromide (XXXVIII) to afford the target intermediate ketone (XLIII).
| 【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 |
|---|---|---|---|---|---|---|
| (XVII) | 42701 | (2S,3R,4S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2,4-dimethyl-5-hexen-3-ol | C14H30O2Si | 详情 | 详情 | |
| (XXXVI) | 42718 | (iodomethyl)(triphenyl)phosphonium iodide | n/a | C19H17I2P | 详情 | 详情 |
| (XXXVIII) | 42720 | bromo(vinyl)zinc | n/a | C2H3BrZn | 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 | |
| (XLIV) | 42723 | tert-butyl(dimethyl)silyl (2S,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl ether; tert-butyl([(2S,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-hexenyl]oxy)dimethylsilane | C22H38O3Si | 详情 | 详情 | |
| (XLV) | 42724 | (2R,3S,4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanal | C21H36O4Si | 详情 | 详情 | |
| (XLVI) | 42725 | (3S,4S,5S)-6-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4-methoxybenzyl)oxy]-3,5-dimethyl-2-hexanol | n/a | C22H40O4Si | 详情 | 详情 |
| (XLVII) | 42726 | (2S,3S,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-1,5-hexanediol | n/a | C16H26O4 | 详情 | 详情 |
| (XLVIII) | 42727 | (2R,3S,4R)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-5-oxohexanal | C16H22O4 | 详情 | 详情 | |
| (XLIX) | 42728 | (3R,4S,5S,6Z)-7-iodo-4-[(4-methoxybenzyl)oxy]-3,5-dimethyl-6-hepten-2-one | C17H23IO3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XLIII)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 |