Baogongteng A
[(1R,4S,5R,7S)-4-羟基-8-氮杂双环[3.2.1]辛烷-7-基]乙酸酯Chemical Name: (-)-6beta-Acetoxy-2beta-hydroxynortropane benzoate; (1R,2S,5R,6S)-6-(Acetyloxy)-2-hydroxy-8-azoniabicyclo[3.2.1]octane benzoate
CAS No. 74239-84-2 (free base)
项目整合开发状态: Phase I
项目研究机构: Shanghai Medical University (Originator)
合成路线:The synthesis of baogongteng A has been published:The alkylation of 3-hydroxypyridine (I) with benzylbromide (II) gives 1-benzyl-3-hydropyridinium bromide (III),which is condensed with acrylonitrile (IV) by means of triethylamine at reflux temperature,yielding the bicyclic nitrile (V).The reduction of (V) with LiAlH4 gives the bicyclic hydroxy nitrile (VII),also obtained by stepwise reduction of (V) with H2 over Pd/C to (VI) and posterior reduction to (VII) with NaBH4.The protection of (VII) with trimethylsilyl chloride and triethylamine affords the silyloxy derivative (VIII),which is treated with methylmagnesium iodide to yield the acetyl derivative (IX).Oxidation of (IX) with m-chloroperbenzoic acid (MCPBA) in CHCl3 affords the acetoxy compound (X),which is finally debenzylated by hydrogenation with H2 and Pd/C in ethanol to give the free base (XI).This is then treated with benzoic acid.
📌 参考资料/链接：
参考文献标题:Total synthesis of Bao Gong Teng-A,a natural antiglaucoma compound
文献作者:Zeng,L.M.; Jung,M.E.; Peng,T.S.; Zeng,H.Y.; Le,Y.; Su,J.Y.
参考来源:J Org Chem 1992,57(13),3528
📄 详细内容
合成路线:The bromination of the acetoxytropanone (I) with Br2 gives the bromo derivative (II),which is treated with Ag2CO3 to yield the hydroxy compound (III).The reaction of (III) with ethane-1,2-dithiol (IV) in acid medium affords the cyclic dithioketal (V),which is desulfurized with H2 over Raney-Ni providing the tropanol derivative (VI).The oxidation of (VI) with CrO3 gives the tropanone derivative (VII),which is stereoselectively reduced with NaBH4,yielding the tropanol compound (VIII).Finally,this compound is demethylated by reaction with 2,2,2-trichloroethyl chloroformate and reduction with Zn and acetic acid.
参考文献标题:Synthesis of biologically active alkaloids of Chinese medicinal herbs
文献作者:Liu,J.
参考来源:Drugs Fut 1994,19(3),265-278
产品链接: CAS No. 74239-84-2››