Stereocontrolled enantioselective total synthesis of the [2+2] quadrigemine alkaloids

TETRAHEDRON

卷:71

Article

Canham, Stephen M.¹  Hafensteiner, Benjamin D.¹  Lebsack, Alec D.¹  May-Dracka, Tricia L.¹  Nam, Sangkil²  Stearns, Brian A.¹  Overman, Larry E.¹ 

[1] Univ Calif Irvine, Dept Chem, Nat Sci 2 1102, Irvine, CA 92697 USA

[2] City Hope Comprehens Canc Ctr, Beckman Res Inst, Dept Mol Med, Duarte, CA 91010 USA

关键词: Stereocontrolled total synthesis;    Alkaloid;    Enantioselective catalysis;    Intramolecular Heck reaction;   

DOI  :  10.1016/j.tet.2015.02.080

来源: Elsevier

【 摘 要 】

A unified strategy for enantioselective total synthesis of all stereoisomers of the [2+2] family of quadrigemine alkaloids is reported. In this approach, two enantioselective intramolecular Heck reactions are carried out at the same time on precursors fashioned in four steps from either meso- or (+)-chimonanthine to form the two critical quaternary carbons of the peripheral cyclotryptamine rings of these products. Useful levels of catalyst control are realized in either desymmetrizing a mesa precursor or controlling diastereoselectivity in elaborating C-2-symmetric intermediates. None of the synthetic quadrigemines are identical with alkaloids isolated previously and referred to as quadrigemines A and E. In addition, we report improvements in our previous total syntheses of (+)- or (-)-quadrigemine C that shortened the synthetic sequence to 10 steps and provided these products in 2.2% overall yield from tryptamine. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

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