The Enantioselective Total Synthesis of Bisquinolizidine Alkaloids: A Modular "Inside-Out" Approach

被引：22

作者：

Scharnagel, Dagmar ^{[1
]}

Goller, Jessica ^{[1
]}

Deibl, Nicklas ^{[2
]}

Milius, Wolfgang ^{[2
]}

Breuning, Matthias ^{[1
]}

机构：

[1] Univ Bayreuth, Organ Chem Lab, Univ Str 30, D-95447 Bayreuth, Germany

[2] Univ Bayreuth, Inorgan Chem Lab, Univ Str 30, D-95447 Bayreuth, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2018年 / 57卷 / 09期

关键词：

alkaloids; bispidine; enantioselectivity; natural products; total synthesis; CHIRAL; 2-ENDO-SUBSTITUTED; 9-OXABISPIDINES; COPPER(II)-CATALYZED HENRY REACTIONS; ASYMMETRIC-SYNTHESIS; SECONDARY ALCOHOLS; LIGANDS; (+/-)-ALPHA-ISOSPARTEINE; (+/-)-BETA-ISOSPARTEINE; FUNCTIONALIZATION; (+)-SPARTEINE; (-)-SPARTEINE;

D O I：

10.1002/anie.201712852

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Bisquinolizidine alkaloids are characterized by a chiral bispidine core (3,7-diazabicyclo[3.3.1]nonane) to which combinations of an alpha,N-fused 2-pyridone, an endo- or exo-alpha,N-annulated piperidin(on)e, and an exo-allyl substituent are attached. We developed a modular inside-out approach that permits access to most members of this class. Its applicability was proven in the asymmetric synthesis of 21 natural bisquinolizidine alkaloids, among them more than ten first enantioselective total syntheses. Key steps are the first successful preparation of both enantiomers of C-2-symmetric 2,6-dioxobispidine by desymmetrization of a 2,4,6,8-tetraoxo precursor, the construction of the alpha,N-fused 2-pyridone by using an enamine-bromoacrylic acid strategy, and the installation of endo- or, optionally, exo-annulated piperidin(on)es.

引用

收藏

页码：2432 / 2435

页数：4

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