A carbonate-forming Baeyer-Villiger monooxygenase

Hu, Youcai; Dietrich, David; Xu, Wei; Patel, Ashay; Thuss, Justin A. J.; Wang, Jingjing; Yin, Wen‐Bing; Qiao, Kangjian; Houk, K. N.; Vederas, John C.; Tang, Yi

doi:10.1038/nchembio.1527

Cited by 79 publications

(73 citation statements)

References 27 publications

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“…While a similar Criegee intermediate can be written for the second oxygen insertion, Scheme 129 depicts a route via epoxy intermediate that might be in play for generation of the unique cyclic carbonate functional group. 577 The mechanism starts with the 1,4-addition of the flavin-peroxo anion onto 912 to yield the adduct 913 . This leads to formation of the epoxide 914 that can ring open to give the α-alkoxide 915.…”

Section: Oxidative Ring Rearrangementmentioning

confidence: 99%

Oxidative Cyclization in Natural Product Biosynthesis

et al. 2016

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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. The 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 installation of epoxides and halogens into acyclic scaffolds to drive subsequent cyclizations are separately discussed as examples of “disappearing” reactive handles. Lastly, oxidative rearrangement of rings systems, including contractions and expansions will be covered.

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Section: Oxidative Ring Rearrangementmentioning

confidence: 99%

Oxidative Cyclization in Natural Product Biosynthesis

et al. 2016

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“…[164] In the presence of FAD, NADPH and a flavin reductase, the recombinant CcsB converts ketocytochalasin ( 176 ) to a lactone iso-precytochalasin ( 178 ) and a carbonate-containing compound cytochalasin Z 16 ( 180 , Figure 46). [165] Iso-precytochalasin ( 178 ) is likely a side-product resulting from the rapid isomerization of the nascent product ( 177 ) from the first oxidation, which is a Baeyer-Villiger reaction. The second oxidation converting an ester to a carbonate moiety through a pseudo -BV mechanism is an intrinsically challenging transformation because the increased electron density on the ester carbonyl renders it less susceptible toward nucleophilic attack.…”

Section: Oxidation and Reduction Reactionsmentioning

confidence: 99%

The Enzymology of Organic Transformations: A Survey of Name Reactions in Biological Systems

2017

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Chemical reactions that are named in honor of their true or at least perceived discoverers are known as “name reactions”. This review is a collection of biological representatives of named chemical reactions. Emphasis is placed on reaction types and catalytic mechanisms that showcase both the chemical diversity in natural product biosynthesis as well as the parallels with synthetic organic chemistry. An attempt has been made to describe the enzymatic mechanisms of catalysis within the context of their synthetic counterparts whenever possible and to discuss the mechanistic hypotheses for those reactions that are presently active areas of investigation. This review has been categorized by reaction type, e.g., condensation, nucleophilic addition, reduction and oxidation, substitution, carboxylation, radical-mediated, and rearrangements, which are subdivided by named reactions.

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“…Cytochalasans have received considerable attention from both chemists and pharmacologists over the past 50 years because of their intriguing structures and potent biological activity, [1] which is exemplified by immunomodulatory, [2] cytotoxic, [3] and nematicidal activity. [4] To date,m ore than 200 cytochalasans have been reported, from various fungi origins,s uch as Chaetomium, Aspergillus,a nd Penicillium species.…”

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Epicochalasines A and B: Two Bioactive Merocytochalasans Bearing Caged Epicoccine Dimer Units from Aspergillus flavipes

et al. 2016

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Two bioactive merocytochalasans, epicochalasines A (1) and B (2), a new class of cytochalasans bearing unexpected scaffolds consisting of fused aspochalasin and epicoccine dimer moieties, were isolated from the liquid culture broth of Aspergillus flavipes. Both 1 and 2 possess a hendecacyclic 5/6/11/5/6/5/6/5/6/6/5 ring system containing an adamantyl cage and as many as 19 stereogenic centers; however, the fusion patterns of 1 and 2 differ greatly, thus resulting in different carbon skeletons. The absolute configurations of 1 and 2 were determined by X-ray diffraction and calculated ECD, respectively. The biogenetic pathways of 1 and 2 are proposed to involve Diels-Alder and nucleophilic addition reactions. Both 1 and 2 induced significant G2/M-phase cell-cycle arrest. Furthermore, we found that merocytochalasans induce apoptosis in leukemia cells through the activation of caspase-3 and the degradation of PARP.

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A carbonate-forming Baeyer-Villiger monooxygenase

Cited by 79 publications

References 27 publications

Oxidative Cyclization in Natural Product Biosynthesis

Oxidative Cyclization in Natural Product Biosynthesis

The Enzymology of Organic Transformations: A Survey of Name Reactions in Biological Systems

Epicochalasines A and B: Two Bioactive Merocytochalasans Bearing Caged Epicoccine Dimer Units from Aspergillus flavipes

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