(+)-Deoxoartelinic acid
Chemical Name: (+)-4-[2-[(3R,5aS,6R,8aS,9R,10R,12R,12aR)-3,6,9-Trimethylperhydro-3,12-epoxypyrano[4,3-j]-1,2-benzodioxepin-10-yl]ethyl]benzoic acid; (+)-10(R)-[2-(4-Carboxyphenyl)ethyl]-10-deoxoartemisinin
CAS No. 150894-00-1 (undefined stereoch.)
项目整合开发状态: Preclinical
项目研究机构: London School Hygiene Tropical Medicine (Originator), Northwick Park Inst. Medical Research (Originator), Yonsei University (Originator)
合成路线:The title compound is prepared starting from artemisinic acid (I),which is extracted from the leaves of Artemisia annua.Esterification of (I) with ethereal diazomethane affords methyl ester (II).Reduction of (II) by means of lithium or sodium borohydride and NiCl2 leads to the saturated ester (III),which is further reduced with DIBAL to the aldehyde (IV).Condensation of (IV) with the sulfur ylide generated from trimethylsulfonium iodide and KOH furnishes epoxide (V).Then,epoxide ring opening with the Grignard reagent (VI) gives alcohol (VII).Photooxigenative cyclization of (VII) produces the artemisinin derivative (VIII).Finally,oxidative vinyl group cleavage employing KMnO4 yields the target carboxylic acid.(1,2)
📌 参考资料/链接：
参考文献标题:Method of preparing (+)-deoxoartemisinin and selected analogues of (+)-deoxoartemisinin
文献作者:McChesney,J.D.; Jung,M.
参考来源:US 5225562
📄 详细内容
合成路线:The title compound is prepared starting from artemisinic acid (I),which is extracted from the leaves of Artemisia annua.Esterification of (I) with ethereal diazomethane affords methyl ester (II).Reduction of (II) by means of lithium or sodium borohydride and NiCl2 leads to the saturated ester (III),which is further reduced with DIBAL to the aldehyde (IV).Condensation of (IV) with the sulfur ylide generated from trimethylsulfonium iodide and KOH furnishes epoxide (V).Then,epoxide ring opening with the Grignard reagent (VI) gives alcohol (VII).Photooxigenative cyclization of (VII) produces the artemisinin derivative (VIII).Finally,oxidative vinyl group cleavage employing KMnO4 yields the target carboxylic acid.(1,2)
参考文献标题:Synthesis,stability,and antimalarial activity of new hydrolytically stable and water-soluble (+)-deoxoartelinic acid
文献作者:Jung,M.; Lee,K.; Kendrick,H.; Robinson,B.L.; Croft,S.L.
参考来源:J Med Chem 2002,45(22),4940