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【结 构 式】

【分子编号】39401

【品名】methyl (5S,7S)-5-hydroxy-7-[(4-methoxybenzyl)oxy]-8,8-dimethyl-3-oxo-10,10-diphenyl-9-decenoate

【CA登记号】

【 分 子 式 】C33H38O6

【 分 子 量 】530.66112

【元素组成】C 74.69% H 7.22% O 18.09%

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:(X)

C1-C9 Fragment: The condensation of 2,2-dimethyl-4,4-diphenyl-3-butenal (I) with the chiral oxazolidinone (II) by means of dibutylboron triflate gives the chiral ketol (III), which is dechlorinated with Zn and AcOH in THF yielding the beta-hydroxyimide (IV). The reduction of (IV) with LiBH4 in methanol/THF affords the chiral diol (V), which is treated with 4-methoxybenzaldehyde dimethyl acetal and PPTS in dichloromethane to give the cyclic ketal (VI). The regioselective reduction of (VI) with DIBAL in dichloromethane yields the monoprotected diol (VII), which is oxidized to aldehyde (VIII) with oxalyl chloride in DMSO. The condensation of (VIII) with the bis(trimethylsilyl)dienol ether (IX) by means of TiCl2(i-PrO)2 in toluene affords the ketoester (X), which by stereoselective reduction with (AcO)3BHNMe4 in acetonitrile/acetic acid gives the dihydroxyester (XI) with high stereoselectivity. The lactonization of (XI) by means of PPTS in refluxing benzene yields the hydroxylactone (XII), which is silylated with TBDMS-OTf and 2,6-lutidine in dichloromethane affording the silylated lactone (XIII). Opening of the lactone ring with aniline and Me3Al in dichloromethane gives the monoprotected dihydroxyamide (XIV), which is ozonolyzed with O3 in CH2Cl2/MeOH yielding the cyclic lactol (XV). Acetylation of (XV) with acetic anhydride and pyridine affords the acetate (XVI), which by reaction with TMS-SPh, ZnI2 and tetrabutylammonium iodide is converted regioselectively into the phenylsulfanyl derivative (XVII). Finally, this compound is oxidized with m-chloroperbenzoic acid (MCPBA) in EtOAc to provide the desired C1-C9 subunit fragment (XVIII).

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
(I) 39392 2,2-dimethyl-4,4-diphenyl-3-butenal C18H18O 详情 详情
(II) 39393 (4S)-4-benzyl-3-(2-chloroacetyl)-1,3-oxazolidin-2-one C12H12ClNO3 详情 详情
(III) 39394 (4S)-4-benzyl-3-[(2S,3R)-2-chloro-3-hydroxy-4,4-dimethyl-6,6-diphenyl-5-hexenoyl]-1,3-oxazolidin-2-one C30H30ClNO4 详情 详情
(IV) 39395 (4S)-4-benzyl-3-[(3S)-3-hydroxy-4,4-dimethyl-6,6-diphenyl-5-hexenoyl]-1,3-oxazolidin-2-one C30H31NO4 详情 详情
(V) 39396 (3S)-4,4-dimethyl-6,6-diphenyl-5-hexene-1,3-diol C20H24O2 详情 详情
(VI) 39397 4-[(4S)-4-(1,1-dimethyl-3,3-diphenyl-2-propenyl)-1,3-dioxan-2-yl]phenyl methyl ether; (4S)-4-(1,1-dimethyl-3,3-diphenyl-2-propenyl)-2-(4-methoxyphenyl)-1,3-dioxane C28H30O3 详情 详情
(VII) 39398 (3S)-3-[(4-methoxybenzyl)oxy]-4,4-dimethyl-6,6-diphenyl-5-hexen-1-ol C28H32O3 详情 详情
(VIII) 39399 (3S)-3-[(4-methoxybenzyl)oxy]-4,4-dimethyl-6,6-diphenyl-5-hexenal C28H30O3 详情 详情
(IX) 39400 (1Z)-1,3-bis[(trimethylsilyl)oxy]-1,3-butadienyl methyl ether; (Z)-4-methoxy-2,2,8,8-tetramethyl-6-methylene-3,7-dioxa-2,8-disila-4-nonene C11H24O3Si2 详情 详情
(X) 39401 methyl (5S,7S)-5-hydroxy-7-[(4-methoxybenzyl)oxy]-8,8-dimethyl-3-oxo-10,10-diphenyl-9-decenoate C33H38O6 详情 详情
(XI) 39402 methyl (3R,5R,7S)-3,5-dihydroxy-7-[(4-methoxybenzyl)oxy]-8,8-dimethyl-10,10-diphenyl-9-decenoate C33H40O6 详情 详情
(XII) 39403 (4R,6R)-4-hydroxy-6-[(2S)-2-[(4-methoxybenzyl)oxy]-3,3-dimethyl-5,5-diphenyl-4-pentenyl]tetrahydro-2H-pyran-2-one C32H36O5 详情 详情
(XIII) 39404 (4R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(2S)-2-[(4-methoxybenzyl)oxy]-3,3-dimethyl-5,5-diphenyl-4-pentenyl]tetrahydro-2H-pyran-2-one C38H50O5Si 详情 详情
(XIV) 39405 (3R,5S,7S)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-7-[(4-methoxybenzyl)oxy]-8,8-dimethyl-N,10,10-triphenyl-9-decenamide C44H57NO5Si 详情 详情
(XV) 39406 (3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(2S,4S)-6-hydroxy-4-[(4-methoxybenzyl)oxy]-5,5-dimethyltetrahydro-2H-pyran-2-yl]-N-phenylbutanamide C31H47NO6Si 详情 详情
(XVI) 39407 (4S,6S)-6-((2R)-4-anilino-2-[[tert-butyl(dimethyl)silyl]oxy]-4-oxobutyl)-4-[(4-methoxybenzyl)oxy]-3,3-dimethyltetrahydro-2H-pyran-2-yl acetate C33H49NO7Si 详情 详情
(XVII) 39408 (3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(2S,4S,6R)-4-[(4-methoxybenzyl)oxy]-5,5-dimethyl-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]-N-phenylbutanamide C37H51NO5SSi 详情 详情
(XVIII) 63864 (3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-[(2S,4S,6R)-4-[(4-methoxybenzyl)oxy]-5,5-dimethyl-6-(phenylsulfonyl)tetrahydro-2H-pyran-2-yl]-N-phenylbutanamide C37H51NO7SSi 详情 详情
Extended Information