Afeletecan hydrochloride, BAY-38-3441
月桂56-3722Chemical Name: N-[4-(6-Deoxy-3-O-methyl-beta-L-galactopyranosyloxy)phenylaminothiocarbonyl]-L-histidyl-L-valine 4(S)-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl ester hydrochloride ; N-[4-(3-O-Methyl-beta-L-fucopyranosyloxy)phenylthiocarbamoyl]-L-histidyl-L-valine camptothecin ester
CAS No. 215604-74-3, 215604-66-3 (diastereomeric mixture), 215604-75-4 (free base)
项目整合开发状态: Phase I
项目研究机构: Bayer (Originator)
合成路线:Acylation of the tertiary 20-hydroxy group of camptothecin (I) with N-Boc-valine-N-carboxyanhydride (II) afforded the corresponding ester (III).Subsequent acidic N-Boc group cleavage gave amino ester (IV).This was coupled with N-Boc-histidine (V) to furnish,after treatment with trifluoroacetic acid,the histidyl-valyl camptothecin ester (VI).
合成路线:Regioselective O-methylation of p-nitrophenyl-beta-L-fucopyranoside (VII) by means of dibutyltin oxide and iodomethane provided the 3-O-methyl pyranoside (VIII).Subsequent catalytic hydrogenation of the nitro group of (VIII) over PtO2 gave aniline (IX),which was further converted to the isothiocyanate (X) upon treatment with thiophosgene and ethyl diisopropylamine.Finally,coupling between isothiocyanate (X) and amine (VI) furnished the target thiourea adduct,which was finally isolated as the corresponding hydrochloride salt.
📌 参考资料/链接：
参考文献标题:20(S) Camptothecin glycoconjugates
文献作者:Baumgarten,J.; Von dem Bruch,K.; Lerchen,H.-G.; Sperzel,M.(Bayer AG)
参考来源:DE 19801037; DE 19813137; EP 0981542; JP 2001526661; WO 9851703
📄 详细内容
合成路线:Acylation of the tertiary 20-hydroxy group of camptothecin (I) with N-Boc-valine-N-carboxyanhydride (II) afforded the corresponding ester (III).Subsequent acidic N-Boc group cleavage gave amino ester (IV).This was coupled with N-Boc-histidine (V) to furnish,after treatment with trifluoroacetic acid,the histidyl-valyl camptothecin ester (VI).
合成路线:Regioselective O-methylation of p-nitrophenyl-beta-L-fucopyranoside (VII) by means of dibutyltin oxide and iodomethane provided the 3-O-methyl pyranoside (VIII).Subsequent catalytic hydrogenation of the nitro group of (VIII) over PtO2 gave aniline (IX),which was further converted to the isothiocyanate (X) upon treatment with thiophosgene and ethyl diisopropylamine.Finally,coupling between isothiocyanate (X) and amine (VI) furnished the target thiourea adduct,which was finally isolated as the corresponding hydrochloride salt.
参考文献标题:Design and optimization of 20-O-linked camptothecin glyconjugates as anticancer agents
文献作者:Lerchen,H.-G.; Baumgarten,J.; von dem Bruch,K.; Lehmann,T.E.; Sperzel,M.; Kempka,G.; Fiebig,H.H.
参考来源:J Med Chem 2001,44(24),4186