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Chem Rev. 2017 Apr 26;117(8):5226-5333. doi: 10.1021/acs.chemrev.6b00478. Epub 2016 Dec 12.

Oxidative Cyclization in Natural Product Biosynthesis.

Author information

1
Department of Chemical and Biomolecular Engineering, and Department of Chemistry and Biochemistry, University of California, Los Angeles , 420 Westwood Plaza, Los Angeles, California 90095, United States.
2
Department of Pharmaceutical Sciences, University of Shizuoka , Shizuoka 422-8526, Japan.
3
Stanford University Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University , 443 Via Ortega, Stanford, California 94305, United States.

Abstract

Oxidative cyclizations are important transformations that occur widely during natural product biosynthesis. The transformations from acyclic precursors to cyclized products can afford morphed scaffolds, structural rigidity, and biological activities. Some of the most dramatic structural alterations in natural product biosynthesis occur through oxidative cyclization. In this Review, we examine the different strategies used by nature to create new intra(inter)molecular bonds via redox chemistry. This Review will cover both oxidation- and reduction-enabled cyclization mechanisms, with an emphasis on the former. Radical cyclizations catalyzed by P450, nonheme iron, α-KG-dependent oxygenases, and radical SAM enzymes are discussed to illustrate the use of molecular oxygen and S-adenosylmethionine to forge new bonds at unactivated sites via one-electron manifolds. Nonradical cyclizations catalyzed by flavin-dependent monooxygenases and NAD(P)H-dependent reductases are covered to show the use of two-electron manifolds in initiating cyclization reactions. The oxidative installations of epoxides and halogens into acyclic scaffolds to drive subsequent cyclizations are separately discussed as examples of "disappearing" reactive handles. Last, oxidative rearrangement of rings systems, including contractions and expansions, will be covered.

PMID:
27936626
PMCID:
PMC5406274
DOI:
10.1021/acs.chemrev.6b00478
[Indexed for MEDLINE]
Free PMC Article

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