新产品编号:1731217
Chemical Name: 1-[[3(R)-Amino-2(S)-sulfanyl-3-(2-sulfoethyl)propionyl]-L-isoleucyl]pyrrolidine-2(S),3(R)-dicarboxylic acid inner salt
项目整合开发状态: Biological Testing
项目研究机构: INSERM (Originator)
合成路线:Esterification of N-(benzyloxycarbonyl)-L-aspartic acid beta-tert-butyl ester (I) by means of diazomethane provided the alpha-methyl ester (II),which was subsequently sulfenylated using (2,4-dinitrophenyl)-(4-methoxybenzyl)disulfide (III) in the presence of n-BuLi to furnish the (2R,3R)-sulfide (IV) as the major isomer.Reduction of the methyl ester group of (IV) with DIBAL,followed by Wittig-Horner reaction of a postulated aldehyde aluminoxyacetal intermediate with neopentyl diethoxyphosphoryl methanesulfonate produced the alpha,beta-unsaturated sulfonate ester (V).Reduction of the double bond of (V) employing [(PPh3)CuH]6 in neutral medium afforded the saturated ester (VI) with only a small epimerization at the C2 position.The tert-butyl ester of (VI) was then deprotected with trifluoroacetic acid yielding the free acid (VII).
合成路线:The resulting free acid (VII) was coupled with the protected dipeptide (VIII) to give tripeptide (IX).Finally,acidic removal of all protecting groups of (IX) provided the title compound.
📌 参考资料/链接：
参考文献标题:Tripeptide cpds.useful as selective inhibitors of aminopeptidase A and corresponding pharmaceutical compsns.
文献作者:Fournie-Zaluski,M.-C.; Roques,B.; David,C.; Bischoff,L.; Llorens-Cortes,C.(CNRS (Centre National de la Recherche Scientifique); INSERM (Institut National de la Sante et de la Recherche Medicale))
参考来源:FR 2788526; WO 0043414
📄 详细内容
合成路线:Esterification of N-(benzyloxycarbonyl)-L-aspartic acid beta-tert-butyl ester (I) by means of diazomethane provided the alpha-methyl ester (II),which was subsequently sulfenylated using (2,4-dinitrophenyl)-(4-methoxybenzyl)disulfide (III) in the presence of n-BuLi to furnish the (2R,3R)-sulfide (IV) as the major isomer.Reduction of the methyl ester group of (IV) with DIBAL,followed by Wittig-Horner reaction of a postulated aldehyde aluminoxyacetal intermediate with neopentyl diethoxyphosphoryl methanesulfonate produced the alpha,beta-unsaturated sulfonate ester (V).Reduction of the double bond of (V) employing [(PPh3)CuH]6 in neutral medium afforded the saturated ester (VI) with only a small epimerization at the C2 position.The tert-butyl ester of (VI) was then deprotected with trifluoroacetic acid yielding the free acid (VII).
合成路线:The resulting free acid (VII) was coupled with the protected dipeptide (VIII) to give tripeptide (IX).Finally,acidic removal of all protecting groups of (IX) provided the title compound.
参考文献标题:Investigation of subsite preferences in aminopeptidase A (EC 3.4.11.7) led to the design of the first highly potent and selective inhibitors of this enzyme
文献作者:Davis,C.; Bischoff,L.; Meudal,H.; Mothe,A.; De Mota,N.; DaNascimento,S.; Llorens-Cortes,C.; Fournie-Zaluski,M.C.; Roques,B.P.
参考来源:J Med Chem 1999,42(25),5197