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【结 构 式】

【分子编号】39428

【品名】(3R)-3-[(4-methoxybenzyl)oxy]-2-butanone

【CA登记号】

【 分 子 式 】C12H16O3

【 分 子 量 】208.25724

【元素组成】C 69.21% H 7.74% O 23.05%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XXXVIII)

C17-C27 Fragment: The monotosylation of 2,2-dimethylpropane-1,3-diol (XXIX) with TsCl and pyridine in CH2Cl2 gives the monotosylate (XXX), which is condensed with thiophenol by means of NaH in hot DMF yielding the phenylsulfanyl derivative (XXXI). The oxidation of (XXXI) with MCPBA in dichloromethane affords the corresponding sulfone (XXXII), which is oxidized with oxalyl chloride in DMSO to give the aldehyde (XXXIII). The Grignard reaction of (XXXIII) with 4-pentenylmagnesium bromide (XXXIV) in ethyl ether/CH2Cl2 yields the secondary alcohol (XXXV), which is oxidized with oxalyl chloride in DMSO to the ketone (XXXVI). The dihydroxylation of the double bond of (XXXVI) with K2OsO4 in t-BuOH/H2O followed by oxidation with NaIO4 in t-BuOH/H2O/THF affords the keto aldehyde (XXXVII), which is condensed with the chiral butanone (XXXVIII) by means of (-)-diisopinocampheyl chloride ((-)-DIP-Cl) and Et3N in dichloromethane to give aldol (XXXIX). The SmI2 catalyzed Tishchenko reduction of (XXXIX) in the presence of 4-nitrobenzaldehyde yields the diastereomerically pure 4-nitrobenzoate (XL), which is silylated with TBDMS-OTf to afford the protected ketone (XLI). The hydrolysis of the 4-nitrobenzoate group of (XLI) with LiOH in THF/MeOH/H2O gives the alcohol (XLII), which is cyclized by means of camphorsulfonic acid (CSA) in refluxing benzene yielding the dihydropyran (XLIII), the desired C17-C27 fragment. The intermediate, the chiral butanone (XXXVIII) has been obtained as follows: The optical resolution of 3-methyl-4-phenyl-3-buten-2-ol (XLIV) with (+)-DIPT gives the (R)-isomer (XLV), which is protected with p-methoxybenzyl bromide and NaH yielding the benzyl ether (XLVI). Finally, (XLVI) is ozonolyzed with O3 in MeOH / CH2Cl2 dichloromethane to afford the desired intermediate (XXXVIII).

1 Lautens, M.; Prunet, J.A.; Carreira, E.M.; Carter, P.H.; Charette, A.B.; Evans, D.A.; Total synthesis of bryostatin 2. J Am Chem Soc 1999, 121, 33, 7540.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXIX) 12641 Neopentyl glycol; 2,2-Dimethyl-1,3-propanediol 126-30-7 C5H12O2 详情 详情
(XXX) 39420 3-hydroxy-2,2-dimethylpropyl 4-methylbenzenesulfonate C12H18O4S 详情 详情
(XXXI) 39421 2,2-dimethyl-3-(phenylsulfanyl)-1-propanol C11H16OS 详情 详情
(XXXII) 39422 2,2-dimethyl-3-(phenylsulfonyl)-1-propanol C11H16O3S 详情 详情
(XXXIII) 39423 2,2-dimethyl-3-(phenylsulfonyl)propanal C11H14O3S 详情 详情
(XXXIV) 39424 bromo(4-pentenyl)magnesium C5H9BrMg 详情 详情
(XXXV) 39425 2,2-dimethyl-1-(phenylsulfonyl)-7-octen-3-ol C16H24O3S 详情 详情
(XXXVI) 39426 2,2-dimethyl-1-(phenylsulfonyl)-7-octen-3-one C16H22O3S 详情 详情
(XXXVII) 39427 6,6-dimethyl-5-oxo-7-(phenylsulfonyl)heptanal C15H20O4S 详情 详情
(XXXVIII) 39428 (3R)-3-[(4-methoxybenzyl)oxy]-2-butanone C12H16O3 详情 详情
(XXXIX) 39429 (7S,10R)-7-hydroxy-10-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1-(phenylsulfonyl)-3,9-undecanedione C27H36O7S 详情 详情
(XL) 39430 (1S)-1-[(2R,3R)-2-hydroxy-3-[(4-methoxybenzyl)oxy]butyl]-6,6-dimethyl-5-oxo-7-(phenylsulfonyl)heptyl 4-nitrobenzoate C34H41NO10S 详情 详情
(XLI) 39431 (1S)-1-[(2R,3R)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]butyl]-6,6-dimethyl-5-oxo-7-(phenylsulfonyl)heptyl 4-nitrobenzoate C40H55NO10SSi 详情 详情
(XLII) 39432 (7S,9R,10R)-9-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-10-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1-(phenylsulfonyl)-3-undecanone C33H52O7SSi 详情 详情
(XLIII) 39433 tert-butyl([(1R,2R)-1-([(2S)-6-[1,1-dimethyl-2-(phenylsulfonyl)ethyl]-3,4-dihydro-2H-pyran-2-yl]methyl)-2-[(4-methoxybenzyl)oxy]propyl]oxy)dimethylsilane; 2-((2S)-2-[(2R,3R)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]butyl]-3,4-dihydro-2H-pyran-6-yl)-2-methylpropyl phenyl sulfone C33H50O6SSi 详情 详情
(XLIV) 39434 (E)-3-methyl-4-phenyl-3-buten-2-ol C11H14O 详情 详情
(XLV) 39435 (2R,3E)-3-methyl-4-phenyl-3-buten-2-ol C11H14O 详情 详情
(XLVI) 39436 (1R,2E)-1,2-dimethyl-3-phenyl-2-propenyl 4-methoxybenzyl ether; 1-([[(1R,2E)-1,2-dimethyl-3-phenyl-2-propenyl]oxy]methyl)-4-methoxybenzene C19H22O2 详情 详情
Extended Information