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. 2015 Nov 18;56(46):6332-6334.
doi: 10.1016/j.tetlet.2015.09.070.

Preparation of a 1,2-isoxazolidine synthon for the synthesis of zetekitoxin AB

Srinivas R Paladugu  1 , Ryan E Looper  1
Affiliations

Preparation of a 1,2-isoxazolidine synthon for the synthesis of zetekitoxin AB

Srinivas R Paladugu et al. Tetrahedron Lett. .

Abstract

A synthesis of the 1,2-isoxazolidine fragment of the potent voltage gated sodium channel blocker, zetekitoxin AB is described. The synthesis utilizes an intramolecular nitrone -olefin 1,3-dipolar cycloaddition to establish the stereochemistry of the cis-1,2-isoxazolidine. The oxidative cleavage of an all anti-triol with the excision of the central carbon is central to using α-D-glucopyranoside as a traceless stereochemical template. This route furnishes a suitably protected synthon for the synthesis of zetekitoxin AB.

Keywords: 1,2-isoxazolidine; Zetikitoxin AB; dipolar cycloaddition; nitrone; saxitoxin.

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Figures

Figure 1
Figure 1
Structures of zetekitoxin AB 1 and saxitoxin 2.
Scheme 1
Scheme 1
The key 1,3-dipolar cycloaddition.
Scheme 2
Scheme 2
Synthesis of a differentially protected diol.
Scheme 3
Scheme 3
Synthesis of a peptide coupling substrate.
See this image and copyright information in PMC

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