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

Xiaolei Wang, Yang Gao, Zhiqiang Ma, Rodrigo A. Rodriguez, Zhi Xiang Yu, Chuo Chen

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)978-984
Number of pages7
JournalOrganic Chemistry Frontiers
Volume2
Issue number8
DOIs
StatePublished - Aug 1 2015

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Pyrroles
Cycloaddition
Biosynthesis
Dimers
Cyclobutanes
Dimerization
Electrons
Cyclization
Biomimetics
Alkaloids
Monomers
sceptrin
nakamuric acid
imidazole
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Syntheses of sceptrins and nakamuric acid and insights into the biosyntheses of pyrrole-imidazole dimers. / Wang, Xiaolei; Gao, Yang; Ma, Zhiqiang; Rodriguez, Rodrigo A.; Yu, Zhi Xiang; Chen, Chuo.

In: Organic Chemistry Frontiers, Vol. 2, No. 8, 01.08.2015, p. 978-984.

Research output: Contribution to journalArticle

Wang, Xiaolei ; Gao, Yang ; Ma, Zhiqiang ; Rodriguez, Rodrigo A. ; Yu, Zhi Xiang ; Chen, Chuo. / Syntheses of sceptrins and nakamuric acid and insights into the biosyntheses of pyrrole-imidazole dimers. In: Organic Chemistry Frontiers. 2015 ; Vol. 2, No. 8. pp. 978-984.
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