Issue 8, 2015

Syntheses of sceptrins and nakamuric acid and insights into the biosyntheses of pyrrole–imidazole dimers

Abstract

Sceptrins and nakamuric acid are structurally unique antibiotics isolated from marine sponges. Recent studies suggest that the biosynthesis of these dimeric pyrrole–imidazole alkaloids involves a single-electron transfer (SET)-promoted [2 + 2] cycloaddition to form their cyclobutane core skeletons. We describe herein the biomimetic syntheses of racemic sceptrin and nakamuric acid. We also report the asymmetric syntheses of sceptrin, bromosceptrin, and dibromosceptrin in their natural enantiomeric form. We further provide mechanistic insights into the pathway selectivity of the SET-promoted [2 + 2] and [4 + 2] cycloadditions that lead to the divergent formation of the sceptrin and ageliferin core skeletons. Both the [2 + 2] and [4 + 2] cycloadditions are stepwise reactions, with the [2 + 2] pathway kinetically and thermodynamically favored over the [4 + 2] pathway. For the [2 + 2] cycloaddition, the dimerization of pyrrole–imidazole monomers is rate-limiting, whereas for the [4 + 2] cycloaddition, the cyclization is the slowest step.

Graphical abstract: Syntheses of sceptrins and nakamuric acid and insights into the biosyntheses of pyrrole–imidazole dimers

Supplementary files

Article information

Article type
Research Article
Submitted
22 Mai 2015
Accepted
12 Jun 2015
First published
12 Jun 2015

Org. Chem. Front., 2015,2, 978-984

Author version available

Syntheses of sceptrins and nakamuric acid and insights into the biosyntheses of pyrrole–imidazole dimers

X. Wang, Y. Gao, Z. Ma, R. A. Rodriguez, Z. Yu and C. Chen, Org. Chem. Front., 2015, 2, 978 DOI: 10.1039/C5QO00165J

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