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【结 构 式】

【分子编号】22729

【品名】benzhydryl (7R)-3-hydroxy-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

【CA登记号】

【 分 子 式 】C28H24N2O5S

【 分 子 量 】500.57504

【元素组成】C 67.18% H 4.83% N 5.6% O 15.98% S 6.41%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XXVIII)

Synthesis of intermediate (II): 2) The esterification of penicillin G (XXI) with diphenylmetbanol and pyridine gives the corresponding ester (XXII), which is oxidized with H2O2 and formic acid to the sulfoxide (XXIII). The reaction of (XXIII) with trimethyl phosphite in refluxing toluene yields the bicyclic thiazoline (XXIV), which is ozonolyzed with O3 in methanol dichloromethane affording the enol (XXV). The condensation of (XXV) with morpholine by means of p-toluenesulfonyl chloride in THF gives the enamine (XXVI), which by bromination with Br2 in pyridine and hydrolysis with H2SO4 in aqueous methanol is converted to diphenylmethyl 7beta-(phenylacetylamino)-3-hydroxy 3-cephem 4-carboxylate (XXVIII) through the intermediate (XXVII).

1 Yoshioka, M.; Synthetic studies related to oral beta-lactam antibiotics. Pure Appl Chem 1987, 59, 8, 1041.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXI) 22722 (2S)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid C16H18N2O4S 详情 详情
(XXII) 22723 benzhydryl (2S)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate C29H28N2O4S 详情 详情
(XXIII) 22724 benzhydryl (2S)-3,3-dimethyl-4,7-dioxo-6-[(2-phenylacetyl)amino]-4lambda(4)-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate C29H28N2O5S 详情 详情
(XXIV) 22725 benzhydryl 2-(3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl)-3-methyl-3-butenoate C29H26N2O3S 详情 详情
(XXV) 22726 benzhydryl (E)-2-(3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl)-3-hydroxy-2-butenoate C28H24N2O4S 详情 详情
(XXVI) 22727 benzhydryl (E)-2-(3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl)-3-(4-morpholinyl)-2-butenoate C32H31N3O4S 详情 详情
(XXVII) 22728 benzhydryl (E)-4-bromo-3-hydroxy-2-[(3R)-2-oxo-3-[(2-phenylacetyl)amino]-4-sulfanylazetidinyl]-2-butenoate C28H25BrN2O5S 详情 详情
(XXVIII) 22729 benzhydryl (7R)-3-hydroxy-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate C28H24N2O5S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XXVIII)

Synthesis of intermediate (II): 2a) The hydrogenation of (XXVIII) with NaBH4 in methanol - dichloromethane yields the cepham derivative (XXIX), which by mesylation with mesyl chloride and hydrolysis with PCl5 and isobutanol is converted to diphenylmethyl 7beta-amino-3-(methanesulfonyloxy)cepham-4-carboxylate (XXX). Finally, this compound is treated with triethylamine or NaHCO3 to obtain the cephem derivative (II). 2b) The elimination of the OH group of (XXVIII) can also be performed by mesylation with mesyl chloride and hydrolysis with PCl5 and isobutanol to give diphenylmethyl 7beta-amino-3-(methanesulfonyloxy)-3-cephem-4-carboxylate (XXXI), which is then treated with Zn in acidic medium to yield cephem derivative (II).

1 Yoshioka, M.; Synthetic studies related to oral beta-lactam antibiotics. Pure Appl Chem 1987, 59, 8, 1041.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II) 22690 benzyl (7R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate C14H14N2O3S 详情 详情
(XXVIII) 22729 benzhydryl (7R)-3-hydroxy-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate C28H24N2O5S 详情 详情
(XXIX) 22730 benzhydryl (7R)-3-hydroxy-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate C28H24N2O5S 详情 详情
(XXX) 22731 benzhydryl (2R,3R,7R)-7-amino-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylate C23H26N2O4S2 详情 详情
(XXXI) 22732 benzhydryl (7R)-7-amino-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate C23H24N2O4S2 详情 详情
Extended Information