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【结 构 式】

【分子编号】63777

【品名】(4R)-4-benzyl-3-(4-ethyl-4-pentenoyl)-1,3-oxazolidin-2-one

【CA登记号】

【 分 子 式 】C17H21NO3

【 分 子 量 】287.35868

【元素组成】C 71.06% H 7.37% N 4.87% O 16.7%

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:(XXVII)

4-Ethylpent-4-enoic acid (XXIV) is coupled to (R)-4-benzyl-2-oxazolidinone (XXV) via its mixed anhydride with pivaloyl chloride, producing the N-acyl oxazolidinone (XXVI). Diastereoselective cyanoethylation of (XXVI) with acrylonitrile leads to (XXVII). Reduction of imide (XXVII) with NaBH4, followed by protection of the resulting alcohol with t-butyldiphenylsilyl chloride furnishes the silyl ether (XXVIII). The nitrile function of (XXVIII) is then reduced by means of DIBAL to the aldehyde (XXIX), which is further treated with hydroxylamine to yield the corresponding oxime (XXX). Exposure of oxime (XXX) to NaOCl generates an intermediate nitrile oxide, which undergoes intramolecular 1,3-dipolar cycloaddition to the isoxazoline (XXXI). Subsequent reductive cleavage of the isoxazoline (XXXI) N-O bond with Zn/AcOH leads to compound (XXXII). Cyclohexanone (XXXII) is then converted to lactone (XXXIII) under Baeyer-Villiger conditions. Further methanolysis of lactone (XXXIII) gives rise to the open-chain dihydroxyester (XXXIV). Sequential protection of the primary hydroxyl group with triethylchlorosilane and the tertiary hydroxyl with trimethylchlorosilane furnishes the fully silylated triol (XXXV) (8). The lithium enolate of ester (XXXV) is then condensed with isothiocyanate (XXXVI) to produce thioanilide (XXXVII) (8, 9).

1 Yokoshima, S.; Ueda, T.; Kobayashi, S.; Sato, A.; Kuboyama, T.; Tokuyama, H.; Fukuyama, T.; Stereocontrolled total synthesis of (+)-vinblastine. J Am Chem Soc 2002, 124, 10, 2137.
2 Schneider, C.; First de novo synthesis of the bisindole alkaloid vinblastine. Angew Chem. Int Ed 2002, 41, 22, 4217.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXV) 63776 4-ethyl-4-pentenoic acid C7H12O2 详情 详情
(XXVI) 14694 (S)-4-Benzyl-2-oxazolidinone; (4S)-4-Benzyl-1,3-oxazolan-2-one; (S)-(-)-4-Benzyl-2-oxazolidinone 90719-32-7 C10H11NO2 详情 详情
(XXVII) 63777 (4R)-4-benzyl-3-(4-ethyl-4-pentenoyl)-1,3-oxazolidin-2-one C17H21NO3 详情 详情
(XXVIII) 63778 (4R)-4-{[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-6-ethyl-6-heptenenitrile C20H24N2O3 详情 详情
(XXIX) 63780 (4R)-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-6-ethyl-6-heptenenitrile C26H35NOSi 详情 详情
(XXX) 63779 (4R)-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-6-ethyl-6-heptenal C26H36O2Si 详情 详情
(XXXI) 63781 (4R)-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-6-ethyl-6-heptenal oxime C26H37NO2Si 详情 详情
(XXXII) 63782 (3aR,5R)-5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-3a-ethyl-3,3a,4,5,6,7-hexahydro-2,1-benzisoxazole; [(3aR,5R)-3a-ethyl-3,3a,4,5,6,7-hexahydro-2,1-benzisoxazol-5-yl]methyl tert-butyl(diphenyl)silyl ether C26H35NO2Si 详情 详情
(XXXIII) 63783 (2S,4R)-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2-ethyl-2-(hydroxymethyl)cyclohexanone C26H36O3Si 详情 详情
(XXXIV) 63784 (5R,7S)-5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-7-ethyl-7-(hydroxymethyl)-2-oxepanone C26H36O4Si 详情 详情
(XXXV) 63785 methyl (4R,6S)-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-6-hydroxy-6-(hydroxymethyl)octanoate C27H40O5Si 详情 详情
(XXXVI) 63788 methyl (4R,6S)-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-6-{[(triethylsilyl)oxy]methyl}-6-[(trimethylsilyl)oxy]octanoate C36H62O5Si3 详情 详情
(XXXVII) 63789 2-[(Z)-3-(tetrahydro-2H-pyran-2-yloxy)-1-propenyl]phenyl isothiocyanate; 2-{[(Z)-3-(2-isothiocyanatophenyl)-2-propenyl]oxy}tetrahydro-2H-pyran C15H17NO2S 详情 详情
(XXXVIII) 63790 methyl (4R,6S)-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2-({2-[(Z)-3-(tetrahydro-2H-pyran-2-yloxy)-1-propenyl]anilino}carbothioyl)-6-{[(triethylsilyl)oxy]methyl}-6-[(trimethylsilyl)oxy]octanoate C51H79NO7SSi3 详情 详情
Extended Information