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Enantioselective synthesis of an ophiobolin sesterterpene via a programmed radical cascade.

ABSTRACT: Cyclase enzymes weave simple polyprenyl chains into the elaborate polycyclic ring systems of terpenes, a sequence that is often difficult to emulate under abiotic conditions. Here we report a disparate synthetic approach to complex terpenes whereby simple prenyl-derived chains are cyclized using radical, rather than cationic, reaction pathways. This strategy allowed us to efficiently forge the intricate 5-8-5 fused ring systems found in numerous complex natural product classes and also enabled a nine-step total synthesis of (-)-6-epi-ophiobolin N, a member of the large family of cytotoxic ophiobolin sesterterpenes. A small-molecule thiol catalyst was found to override the inherent diastereoselectivity observed during a reductive radical cascade cyclization process. This work lays the foundation for efficient synthesis of terpenoid ring systems of interest in medicinal research, particularly those that have been historically challenging to access.

SUBMITTER: Brill ZG

PROVIDER: S-EPMC5319821 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Enantioselective synthesis of an ophiobolin sesterterpene via a programmed radical cascade.

Brill Zachary G ZG Grover Huck K HK Maimone Thomas J TJ

Science (New York, N.Y.) 20160501 6289

Cyclase enzymes weave simple polyprenyl chains into the elaborate polycyclic ring systems of terpenes, a sequence that is often difficult to emulate under abiotic conditions. Here we report a disparate synthetic approach to complex terpenes whereby simple prenyl-derived chains are cyclized using radical, rather than cationic, reaction pathways. This strategy allowed us to efficiently forge the intricate 5-8-5 fused ring systems found in numerous complex natural product classes and also enabled a ...[more]

PMID: 27230373

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