An Efficient Total Synthesis of (-)-Huperzine A

被引：50
作者：
Ding, Rui [1 ]
Sun, Bing-Feng [1 ]
Lin, Guo-Qiang [1 ]
机构：
[1] Chinese Acad Sci, Shanghai Inst Organ Chem, CAS Key Lab Synthet Chem Nat Subst, Shanghai 200032, Peoples R China
来源：
ORGANIC LETTERS | 2012年 / 14卷 / 17期
基金：
中国国家自然科学基金;
关键词：
HUPERZINE-A; ENANTIOSELECTIVE SYNTHESIS; FORMAL SYNTHESIS; CORE STRUCTURE; ALKALOIDS; ROUTE; ACETYLCHOLINESTERASE; CYCLIZATION; ANNULATION; ARYLATION;
D O I：
10.1021/ol301951r
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
The total synthesis of Lycopodium alkaloid (-)-huperzine A has been accomplished in 10 steps with 17% overall yield from commercially abundant (R)-pulegone. The synthetic route features an efficient synthesis of 4 via a Buchwald-Hartwig coupling reaction, a dianion-mediated highly stereoselective alkylation of 4, and a rare example of an intramolecular Heck reaction of an enamine-type substrate. The stereoselective beta-elimination and the accompanying Wagner-Meerwein rearrangement are of particular interest.
引用
收藏
页码：4446 / 4449
页数：4
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共 52 条
  • [1] DEMENTIA A problem for our age
    Abbott, Alison
    [J]. NATURE, 2011, 475 (7355) : S2 - S4
  • [2] ALKALOIDS OF LYCOPODIUM-SELAGO - ON THE IDENTITY OF SELAGINE WITH HUPERZINE-A AND THE STRUCTURE OF A RELATED ALKALOID
    AYER, WA
    BROWNE, LM
    ORSZANSKA, H
    VALENTA, Z
    LIU, JS
    [J]. CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1989, 67 (10): : 1538 - 1540
  • [3] Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease
    Bai, DL
    Tang, XC
    He, XC
    [J]. CURRENT MEDICINAL CHEMISTRY, 2000, 7 (03) : 355 - 374
  • [4] Development of huperzine A and B for treatment of Alzheimer's disease
    Bai, Donglu
    [J]. PURE AND APPLIED CHEMISTRY, 2007, 79 (04) : 469 - 479
  • [5] A PALLADIUM-CATALYZED ROUTE TO HUPERZINE-A AND ITS ANALOGS AND THEIR ANTICHOLINESTERASE ACTIVITY
    CAMPIANI, G
    SUN, LQ
    KOZIKOWSKI, AP
    AAGAARD, P
    MCKINNEY, M
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (27) : 7660 - 7669
  • [6] Asymmetric palladium annulation: formal synthesis of (+)-huperzine A
    Chassaing, C
    Haudrechy, A
    Langlois, Y
    [J]. TETRAHEDRON LETTERS, 1999, 40 (50) : 8805 - 8809
  • [7] [+]-Huperzine A treatment protects against N-methyl-D-aspartate-induced seizure/status epilepticus in rats
    Coleman, Brian R.
    Ratcliffe, Ruthie H.
    Oguntayo, Samuel A.
    Shi, Xuerong
    Doctor, Bhupendra P.
    Gordon, Richard K.
    Nambiar, Madhusoodana P.
    [J]. CHEMICO-BIOLOGICAL INTERACTIONS, 2008, 175 (1-3) : 387 - 395
  • [8] Total synthesis of ecteinascidin 743
    Endo, A
    Yanagisawa, A
    Abe, M
    Tohma, S
    Kan, T
    Fukuyama, T
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (23) : 6552 - 6554
  • [9] The cholinergic hypothesis of Alzheimer's disease: a review of progress
    Francis, PT
    Palmer, AM
    Snape, M
    Wilcock, GK
    [J]. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1999, 66 (02) : 137 - 147
  • [10] DRUGS A tangled web of targets
    Gravitz, Lauren
    [J]. NATURE, 2011, 475 (7355) : S9 - S11
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