【结 构 式】 |
【分子编号】39394 【品名】(4S)-4-benzyl-3-[(2S,3R)-2-chloro-3-hydroxy-4,4-dimethyl-6,6-diphenyl-5-hexenoyl]-1,3-oxazolidin-2-one 【CA登记号】 |
【 分 子 式 】C30H30ClNO4 【 分 子 量 】504.02524 【元素组成】C 71.49% H 6% Cl 7.03% N 2.78% O 12.7% |
合成路线1
该中间体在本合成路线中的序号:(III)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 |