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. 2018 Jun;74(26):3188-3197.
doi: 10.1016/j.tet.2018.04.050. Epub 2018 Apr 18.

A convergent approach to batzelladine alkaloids. Total syntheses of (+)-batzelladine E, (-)-dehydrobatzelladine C, and (+)-batzelladine K

Christos Economou  1 , Justin P Romaire  1 , Tony Z Scott  1 , Brendan T Parr  1 , Seth B Herzon  1   2
Affiliations

A convergent approach to batzelladine alkaloids. Total syntheses of (+)-batzelladine E, (-)-dehydrobatzelladine C, and (+)-batzelladine K

Christos Economou et al. Tetrahedron. 2018 Jun.

Abstract

We recently reported a convergent strategy to access the polycyclic guanidinium alkaloid (+)-batzelladine B via an aldol addition-retro-aldol-aza-Michael addition cascade. Here we describe the application of this approach toward the total syntheses of (+)-batzelladine E, (-)-dehydrobatzelladine C, and (+)-batzelladine K. The identification of suitable methods to functionalize a common tropane core by electrophilic alkynylation and nucleophilic 1,2-addition were essential to generalizing this approach. We provide evidence for the intermediacy of an acylallene species in the cascade reaction.

Keywords: Alkaloid; Batzelladine; Dehydrobatzelladine; Total synthesis; Tropane.

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Figures

Fig. 1.
Fig. 1.
Structures of (+)-batzelladine A (1), (−)-batzelladine D (2), (+)-batzelladine B (3), (+)-batzelladine E (4), (−)-dehydrobatzelladine C (5), and (+)-batzelladine K (6).
Scheme 1.
Scheme 1.
A. Synthesis of the bicyclic guanidine 13, a precursor to (+)-batzelladine B (3), via an aldol addition–retro-aldol–aza-Michael addition cascade. B. Outline of a general synthetic strategy toward syn-pyrrolidine guanidinium natural products.
Scheme 2.
Scheme 2.
Synthesis of the α-alkynyl-β-ketoester 18.
Scheme 3.
Scheme 3.
Synthesis of the bicyclic guanidines 20a–c.
Scheme 4.
Scheme 4.
Completion of the total syntheses of (+)-batzelladine K (6), (+)-batzelladine E (4), and (−)-dehydrobatzelladine C (5).
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