-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】(1R,5S,6S)-2-[5(S)-[3(S),4(S)-Dihydroxypyrrolidin-1-ylcarbonyl]pyrrolidin-3(S)-ylsulfanyl]-6-[1(R)-hydroxyethyl]-1-methyl-1-carba-2-penem-3-carboxylic acid

【CA登记号】

【分子式】C₁₉H₂₇N₃O₇S

【分子量】441.50694

【开发单位】Korea Inst. Sci. Technol. (Originator), Korea Res. Inst. Chem. Technol. (Originator)

【药理作用】Antibiotics, ANTIINFECTIVE THERAPY, Carbapenems

合成路线1

L-Tartaric acid (I) was converted to succinimimide (II) upon treatment with benzylamine in refluxing xylene with azeotropic removal of water. Subsequent reduction of (II) with borane, generated from NaBH4 and BF3, afforded pyrrolidine (III). Removal of the N-benzyl group of (III) was effected by hydrogenolysis over Pd/C, and the resulting secondary amine (IV) was coupled with the N-protected 3-thioacetylproline (V) to furnish amide (VI). Deacetylation of (VI) under basic conditions provided thiol (VII). Condensation of thiol (VII) with carbapenem enolphosphate (VIII) afforded thioether (IX). The 4-nitrobenzyl protecting groups of (IX) were finally removed by hydrogenolysis over Pd/C.

参考文献中间体

【1】 Park, S.W.; Park, S.Y.; Kim, D.J.; Shin, K.J.; Kang, Y.K.; Yoo, K.H.; Jae Seo, K.; Synthesis and biological evaluation of novel 1beta-methylcarbapenems having a new moiety at C-2. Bioorg Med Chem Lett 1999, 9, 16, 2385.

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)	16695	(2S,3S)-2,3-dihydroxybutanedioic acid; D-(-)-Tartaric Acid; D-Tartaric Acid; (2S,3S)-2,3-dihydroxysuccinic acid	147-71-7	C₄H₆O₆	详情	详情
(II)	33017	(3R,4R)-1-benzyl-3,4-dihydroxy-2,5-pyrrolidinedione	75172-31-5	C₁₁H₁₁NO₄	详情	详情
(III)	33018	(3S,4S)-1-benzyl-3,4-pyrrolidinediol		C₁₁H₁₅NO₂	详情	详情
(IV)	33019	(3S,4S)-3,4-pyrrolidinediol		C₄H₉NO₂	详情	详情
(V)	18241	(2S,4S)-4-(acetylsulfanyl)-1-[[(4-nitrobenzyl)oxy]carbonyl]-2-pyrrolidinecarboxylic acid		C₁₅H₁₆N₂O₇S	详情	详情
(VI)	33020	4-nitrobenzyl (2S,4S)-4-(acetylsulfanyl)-2-[[(3S,4S)-3,4-dihydroxypyrrolidinyl]carbonyl]-1-pyrrolidinecarboxylate		C₁₉H₂₃N₃O₈S	详情	详情
(VII)	33021	4-nitrobenzyl (2S,4S)-2-[[(3S,4S)-3,4-dihydroxypyrrolidinyl]carbonyl]-4-sulfanyl-1-pyrrolidinecarboxylate		C₁₇H₂₁N₃O₇S	详情	详情
(VIII)	13224	4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	90776-59-3	C₂₉H₂₇N₂O₁₀P	详情	详情
(IX)	33022	4-nitrobenzyl (4R,5S,6S)-3-[((3S,5S)-5-[[(3S,4S)-3,4-dihydroxypyrrolidinyl]carbonyl]-1-[[(4-nitrobenzyl)oxy]carbonyl]pyrrolidinyl)sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₃₄H₃₇N₅O₁₃S	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)