• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】11404

【品名】methyl (1R,9S)-13-[(E)ethylidene]-5-methoxy-11-methylene-6-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-triene-1-carboxylate

【CA登记号】

【 分 子 式 】C18H21NO3

【 分 子 量 】299.36968

【元素组成】C 72.22% H 7.07% N 4.68% O 16.03%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(V)

A new synthesis of huperzine A has been described: The cyclization of 6-hydroxy-2-methoxy-7,8-dihydroquinoline-5-carboxylic acid methyl ester (I) with 2-methylene-1,3-propanediol diacetate (II) by means of palladium diacetate and triphenylphosphine in dioxane gives the tricyclic ketone (III), which is treated with ethyl triphenylphosphonium bromide and butyllithium in THF to yield the corresponding (Z)-ethylidene derivative (IV). Isomerization of (IV) with AIBN and thiophenol in hot toluene affords the (E)-isomer (V), which is hydrolyzed with NaOH to the free acid (VI). The reaction of acid (VI) with diphenyl phosphorazidate and triethylamine gives the carbamic acid ester (VII), which is finally deprotected and isomerized to huperzine A with trimethylsilyl bromide in refluxing CHCl3, followed by a treatment with trifluoromethanesulfonic acid in hot dioxane.

1 Sun, L.Q.; Kozikowski, A.P.; Campiani, G.; Aagaard, P.; McKinney, M.; A palladium-catalyzed route to huperzine-A and its analogues and their anticholinesterase activity. J Org Chem 1993, 58, 27, 7660.
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) 11400 methyl 6-hydroxy-2-methoxy-7,8-dihydro-5-quinolinecarboxylate C12H13NO4 详情 详情
(II) 11401 2-[(acetoxy)methyl]-2-propenyl acetate C8H12O4 详情 详情
(III) 11402 methyl (1S,9S)-5-methoxy-11-methylene-13-oxo-6-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-triene-1-carboxylate C16H17NO4 详情 详情
(IV) 11403 methyl (1R,9S)-13-[(Z)ethylidene]-5-methoxy-11-methylene-6-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-triene-1-carboxylate C18H21NO3 详情 详情
(V) 11404 methyl (1R,9S)-13-[(E)ethylidene]-5-methoxy-11-methylene-6-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-triene-1-carboxylate C18H21NO3 详情 详情
(VI) 11405 (1R,9S)-13-[(E)Ethylidene]-5-methoxy-11-methylene-6-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-triene-1-carboxylic acid C17H19NO3 详情 详情
(VII) 11406 methyl N-[(9S)-13-[(E)ethylidene]-5-methoxy-11-methylene-6-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-trien-1-yl]carbamate C18H22N2O3 详情 详情
Extended Information