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【结 构 式】 
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【分子编号】22732 【品名】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 【CA登记号】 |
【 分 子 式 】C23H24N2O4S2 【 分 子 量 】456.58664 【元素组成】C 60.5% H 5.3% N 6.14% O 14.02% S 14.05% |
合成路线1
该中间体在本合成路线中的序号：(XXXI)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 |
合成路线2
该中间体在本合成路线中的序号：(XXII)Cycloaddition of ethyl diazoacetate to furan (XXII) in the presence of dirhodium tetraacetate gave bicyclic compound (XXIII). Hydroboration of the olefin group of (XXIII) with tert-hexylborane, followed by oxidative treatment with hydrogen peroxide provided alcohol (XXIV), which was oxidized to ketone (IX) under Swern conditions. The title compound was then obtained as above by formation of hydantoin (X), ester hydrolysis, resolution as before, and hydrolysis of the hydantoin.
| 【1】 Massey, S.M.; Monn, J.A.; Valli, M.J. (Eli Lilly and Company); Excitatory amino acid derivs.. US 5688826 . |
| 【2】 Massey, S.M.; Monn, J.A.; Valli, M.J. (Eli Lilly and Company); Excitatory amino acid derivs.. EP 0774461; JP 2000500748; WO 9718199 . |
| 【3】 Levine, L.R. (Eli Lilly and Company); Treatment for premenstrual dysphoric disorder. WO 9832436 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 30108 | (1,1,2-trimethylpropyl)borane | C6H15B | 详情 | 详情 | ||
| (IX) | 30095 | ethyl 4-oxo-2-oxabicyclo[3.1.0]hexane-6-carboxylate | C8H10O4 | 详情 | 详情 | |
| (X) | 30110 | 2,5-Dioxospiro[imidazolidine-4,4'-[2]oxabicyclo[3,1,0]hexane]-6'-carboxylic acid ethyl ester | C10H12N2O5 | 详情 | 详情 | |
| (XXII) | 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 | |
| (XXIII) | 30107 | ethyl 2-oxabicyclo[3.1.0]hex-3-ene-6-carboxylate | C8H10O3 | 详情 | 详情 | |
| (XXIV) | 30109 | ethyl (4R)-4-hydroxy-2-oxabicyclo[3.1.0]hexane-6-carboxylate | C8H12O4 | 详情 | 详情 |