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. 2013 May 3:9:860-5.
doi: 10.3762/bjoc.9.99. Print 2013.

Formal synthesis of (-)-agelastatin A: an iron(II)-mediated cyclization strategy

Daisuke Shigeoka  1 , Takuma Kamon, Takehiko Yoshimitsu
Affiliations

Formal synthesis of (-)-agelastatin A: an iron(II)-mediated cyclization strategy

Daisuke Shigeoka et al. Beilstein J Org Chem. .

Abstract

An iron(II)-mediated aminohalogenation of a cyclopentenyl N-tosyloxycarbamate provided new access to the key intermediate for the synthesis of (-)-agelastatin A (AA, 1), a potent antiproliferative alkaloid. The present synthetic endeavour offered an insight into the mechanism underlying the iron(II)-mediated aminohalogenation of N-tosyloxycarbamate, in which the radical properties of the N-iron intermediates in the redox states were operative.

Keywords: agelastatin; aminohalogenation; free radical; iron(II); natural product synthesis.

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Figures

Scheme 1
Scheme 1
Our first- [26] and second-generation [27] approaches to (−)-agelastatin A (1).
Scheme 2
Scheme 2
The present iron(II)-mediated aminohalogenation of N-tosyloxycarbamate 8 providing key intermediates 5a/5b for (−)-agelastatin A synthesis.
Scheme 3
Scheme 3
Aminohalogenation of azidoformate 3 (2 g scale) under FeBr2/Bu4NBr conditions.
Figure 1
Figure 1
Byproducts formed by aminohalogenation of N-tosyloxycarbamate 8 with FeCl2/TMSCl in EtOH (see Table 1; entry 7).
Scheme 4
Scheme 4
Plausible reaction pathways in the aminohalogenation of N-tosyloxycarbamate 8 with FeX2/Bu4NX.
Scheme 5
Scheme 5
Plausible reaction pathway to produce compounds 9 and 10.
See this image and copyright information in PMC

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