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【结 构 式】 
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【分子编号】43611 【品名】(3S)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-3-phenyl-1H-pyrrolo[1,2-c][1,3]oxazole; tert-butyl(dimethyl)silyl (3S)-6-methyl-3-phenyl-1H-pyrrolo[1,2-c][1,3]oxazol-5-yl ether 【CA登记号】 |
【 分 子 式 】C19H27NO2Si 【 分 子 量 】329.51442 【元素组成】C 69.26% H 8.26% N 4.25% O 9.71% Si 8.52% |
合成路线1
该中间体在本合成路线中的序号：(XXXI)Methylation of bicyclic oxazolidine (XXIX) by means of LDA and MeI, followed by selenenylation with PhSeBr/LDA in THF and ozonolysis in CH2Cl2, affords unsaturated derivative (XXX). Treatment of (XXX) with Tbdms-OTf and 2,6-lutidine in CH2Cl2 yields silyloxypyrrole (XXXI), which is converted into (XXXII) by an aldol reaction with (II) in the presence of SnCl4 in Et2O. Acetylation of (XXXII) by means of Ac2O, pyridine followed by dihydroxylation with OsO4 and N-methylmorpholine N-oxide allows formation of diol (XXXIII), whose tertiary hydroxyl group is removed by means of N,N'-thiocarbonyldiimidazole, followed by reduction with Bu3SnH and catalytic AIBN in toluene to provide derivative (XXXIV). Treatment of (XXXIV) with NaOH in MeOH followed by hydrogenolysis over Pd/C in HCl yields derivative (XXXV), which is converted into (XXXVI) by protection of primary alcohol by means of Et3SiCl and acetylation of secondary alcohol by treatment with Ac2O in pyridine. Regeneration of primary alcohol by treatment of (XXXVI) with HF in CH3CN furnishes (XXXVII), which is then oxidized by means of Jones reagent to yield (XXXVIII). Finally, saponification of diacetate acid (XXXVIII) with NaOH gives lactam (X).
| 【1】 Uno, H.; et al.; Stereocontrolled Mukaiyama-type aldol reaction of siloxypyrroles derived from (S)-glutamic acid. Synlett 1997, 390. |
| 【2】 Uno, H.; et al.; Total synthesis of (+)-lactacystin from (R)-glutamate. J Am Chem Soc 1994, 116, 5, 2139. |
| 【3】 Corey, E.J.; Li, W.-D.Z.; Total synthesis and biological activity of lactacystin, omuralide and analogs. Chem Pharm Bull 1999, 47, 1, 1. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIVa) | 43614 | (1S)-1-[(3S,6S,7S)-7-hydroxy-6-methyl-5-oxo-3-phenyldihydro-1H-pyrrolo[1,2-c][1,3]oxazol-7(5H)-yl]-2-methylpropyl acetate | C19H25NO5 | 详情 | 详情 | |
| (XXXIVb) | 43615 | (1S)-1-[(3S,6R,7S)-7-hydroxy-6-methyl-5-oxo-3-phenyldihydro-1H-pyrrolo[1,2-c][1,3]oxazol-7(5H)-yl]-2-methylpropyl acetate | C19H25NO5 | 详情 | 详情 | |
| (II) | 13226 | 2-Methylpropanal; Isobutyraldehyde | 78-84-2 | C4H8O | 详情 | 详情 |
| (X) | 43590 | (2R,3S,4R)-3-hydroxy-2-[(1S)-1-hydroxy-2-methylpropyl]-4-methyl-5-oxo-2-pyrrolidinecarboxylic acid | C10H17NO5 | 详情 | 详情 | |
| (XXIX) | 43653 | (3S,7aR)-3-phenyltetrahydro-5H-pyrrolo[1,2-c][1,3]oxazol-5-one | C12H13NO2 | 详情 | 详情 | |
| (XXX) | 43610 | (3S,7aR)-6-methyl-3-phenyl-1,7a-dihydro-5H-pyrrolo[1,2-c][1,3]oxazol-5-one | C13H13NO2 | 详情 | 详情 | |
| (XXXI) | 43611 | (3S)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-3-phenyl-1H-pyrrolo[1,2-c][1,3]oxazole; tert-butyl(dimethyl)silyl (3S)-6-methyl-3-phenyl-1H-pyrrolo[1,2-c][1,3]oxazol-5-yl ether | C19H27NO2Si | 详情 | 详情 | |
| (XXXII) | 43612 | (3S,7aR)-7a-[(1S)-1-hydroxy-2-methylpropyl]-6-methyl-3-phenyl-1,7a-dihydro-5H-pyrrolo[1,2-c][1,3]oxazol-5-one | C17H21NO3 | 详情 | 详情 | |
| (XXXIII) | 43613 | (1S)-1-[(3S,6R,7R)-6,7-dihydroxy-6-methyl-5-oxo-3-phenyldihydro-1H-pyrrolo[1,2-c][1,3]oxazol-7(5H)-yl]-2-methylpropyl acetate | C19H25NO6 | 详情 | 详情 | |
| (XXXV) | 43616 | (1S)-1-[(2S,3S,4R)-3-hydroxy-2-(hydroxymethyl)-4-methyl-5-oxopyrrolidinyl]-2-methylpropyl acetate | C12H21NO5 | 详情 | 详情 | |
| (XXXVI) | 43617 | (1S)-1-((2R,3S,4R)-3-(acetoxy)-4-methyl-5-oxo-2-[[(triethylsilyl)oxy]methyl]pyrrolidinyl)-2-methylpropyl acetate | C20H37NO6Si | 详情 | 详情 | |
| (XXXVII) | 43618 | (1S)-1-[(2R,3S,4R)-3-(acetoxy)-2-(hydroxymethyl)-4-methyl-5-oxopyrrolidinyl]-2-methylpropyl acetate | C14H23NO6 | 详情 | 详情 | |
| (XXXVIII) | 43619 | (2R,3S,4R)-3-(acetoxy)-2-[(1S)-1-(acetoxy)-2-methylpropyl]-4-methyl-5-oxo-2-pyrrolidinecarboxylic acid | C14H21NO7 | 详情 | 详情 |