A retro Baeyer-Villiger reaction: electrochemical reduction of [60]fullerene-fused lactones to [60]fullerene-fused ketones.
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ABSTRACT:
SUBMITTER: Niu C
PROVIDER: S-EPMC6427942 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We report a peptide-based catalyst that can strongly influence the regio- and enantioselectivity of the Baeyer-Villiger (BV) oxidation of cyclic ketones bearing amide, urea, or sulfonamide functional groups. Both types of selectivity are thought to arise from a catalyst-substrate hydrogen-bonding interaction. Furthermore, in selected cases, the reactions exhibit the hallmarks of parallel kinetic resolution. The capacity to use catalysis to select between BV products during an asymmetric process may have broad utility for both the synthesis and diversification of complex molecules, including natural products.
| S-EPMC4195385 | biostudies-literature
Project description:The Dakin and Baeyer-Villiger (BV) oxidation reactions require addition of peroxides as oxidants and an acid or a base as a catalyst. Reaction times range from hours to days to obtain target products. Previously, we reported that hydrogen peroxide (H2O2) is spontaneously generated in water microdroplets without any added chemicals or applied electrical potential. Here, we report that the Dakin and BV reactions occur in modest yields within milliseconds in aqueous microdroplets at room-temperature without the addition of external peroxides and catalysts. H2O2 generation is the result of the special environment of the microdroplet surface, which promotes water autoionization. We find that increasing the content of water and decreasing the droplet size improve the product yield of the Dakin and BV reactions, supporting the contention that the amount of H2O2 generated in aqueous microdroplets could induce the two reactions and the reactions occur at or near the air-water interface of the microdroplet surface.
| S-EPMC7439776 | biostudies-literature
Project description:Baeyer-Villiger monooxygenases (BVMOs) are biocatalysts that offer the prospect of high chemo-, regio-, and enantioselectivity in the organic synthesis of lactones or esters from a variety of ketones. In this study, we have cloned, sequenced, and overexpressed in Escherichia coli a new BVMO, cyclopentadecanone monooxygenase (CpdB or CPDMO), originally derived from Pseudomonas sp. strain HI-70. The 601-residue primary structure of CpdB revealed only 29% to 50% sequence identity to those of known BVMOs. A new sequence motif, characterized by a cluster of charged residues, was identified in a subset of BVMO sequences that contain an N-terminal extension of approximately 60 to 147 amino acids. The 64-kDa CPDMO enzyme was purified to apparent homogeneity, providing a specific activity of 3.94 micromol/min/mg protein and a 20% yield. CPDMO is monomeric and NADPH dependent and contains approximately 1 mol flavin adenine dinucleotide per mole of protein. A deletion mutant suggested the importance of the N-terminal 54 amino acids to CPDMO activity. In addition, a Ser261Ala substitution in a Rossmann fold motif resulted in an improved stability and increased affinity of the enzyme towards NADPH compared to the wild-type enzyme (K(m) = 8 microM versus K(m) = 24 microM). Substrate profiling indicated that CPDMO is unusual among known BVMOs in being able to accommodate and oxidize both large and small ring substrates that include C(11) to C(15) ketones, methyl-substituted C(5) and C(6) ketones, and bicyclic ketones, such as decalone and beta-tetralone. CPDMO has the highest affinity (K(m) = 5.8 microM) and the highest catalytic efficiency (k(cat)/K(m) ratio of 7.2 x 10(5) M(-1) s(-1)) toward cyclopentadecanone, hence the Cpd designation. A number of whole-cell biotransformations were carried out, and as a result, CPDMO was found to have an excellent enantioselectivity (E > 200) as well as 99% S-selectivity toward 2-methylcyclohexanone for the production of 7-methyl-2-oxepanone, a potentially valuable chiral building block. Although showing a modest selectivity (E = 5.8), macrolactone formation of 15-hexadecanolide from the kinetic resolution of 2-methylcyclopentadecanone using CPDMO was also demonstrated.
| S-EPMC1449013 | biostudies-literature
Project description:Baeyer-Villiger oxidation of racemic bicyclic cyclobutanones with Zr[bis(salicylidene)ethylenediaminato] (salen) complex 1 as catalyst in the presence of a urea-hydrogen peroxide adduct was found to proceed enantiospecifically. The enantiotopos selection in the oxidation was governed primarily by the Zr(salen) catalyst, although migratory aptitude (methine > methylene > methyl) in Baeyer-Villiger oxidation affected the selection to a varied extent, depending on the substrate structures; one enantiomer of cyclobutanones gave exclusively a normal lactone expected from the migratory aptitude, and the other enantiomer gave an abnormal lactone preferentially, the formation of which is counter to the migratory aptitude. Furthermore, the rates of abnormal lactone formation were found to be faster than those of normal lactone formation in most of the oxidations examined. For example, the enantiomer of racemic bicyclo[3.2.0]heptan-6-one giving an abnormal lactone reacted 2.2 times faster than the other enantiomer giving a normal lactone. To our knowledge, this example of chemocatalytic Baeyer-Villiger oxidation giving an abnormal lactone in preference to a normal lactone has been previously unreported. This unusual behavior is likely to be attributable to strict control of stereoelectronic demand in Baeyer-Villiger oxidation and chiral recognition by complex 1.
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Project description:GilOII has been unambiguously identified as the key enzyme performing the crucial C-C bond cleavage reaction responsible for the unique rearrangement of a benz[a]anthracene skeleton to the benzo[d]naphthopyranone backbone typical of the gilvocarcin-type natural anticancer antibiotics. Further investigations of this enzyme led to the isolation of a hydroxyoxepinone intermediate, leading to important conclusions regarding the cleavage mechanism.
| S-EPMC3498853 | biostudies-literature
Project description:A general question in biochemistry is the interplay between the chemical properties of cofactors and the surrounding protein matrix. Here, the functions of NADP+ and FAD are explored by investigation of a representative monooxygenase reconstituted with chemically-modified cofactor analogues. Like pieces of a jigsaw puzzle, the enzyme active site juxtaposes the flavin and nicotinamide rings, harnessing their H-bonding and steric properties to finely construct an oxygen-reacting center that restrains the flavin-peroxide intermediate in a catalytically-competent orientation. Strikingly, the regio- and stereoselectivities of the reaction are essentially unaffected by cofactor modifications. These observations indicate a remarkable robustness of this complex multi-cofactor active site, which has implications for enzyme design based on cofactor engineering approaches.
| S-EPMC3893305 | biostudies-literature
Project description:Despite the remarkable versatility displayed by flavin-dependent monooxygenases (FMOs) in natural product biosynthesis, one notably missing activity is the oxidative generation of carbonate functional groups. We describe a multifunctional Baeyer-Villiger monooxygenase, CcsB, which catalyzes the formation of an in-line carbonate in the macrocyclic portion of cytochalasin E. This study expands the repertoire of activities of FMOs and provides a possible synthetic strategy for transformation of ketones into carbonates.
| S-EPMC4062580 | biostudies-other
Project description:Flavin-containing Baeyer-Villiger monooxygenases employ NADPH and molecular oxygen to catalyze the insertion of an oxygen atom into a carbon-carbon bond of a carbonylic substrate. These enzymes can potentially be exploited in a variety of biocatalytic applications given the wide use of Baeyer-Villiger reactions in synthetic organic chemistry. The catalytic activity of these enzymes involves the formation of two crucial intermediates: a flavin peroxide generated by the reaction of the reduced flavin with molecular oxygen and the "Criegee" intermediate resulting from the attack of the flavin peroxide onto the substrate that is being oxygenated. The crystal structure of phenylacetone monooxygenase, a Baeyer-Villiger monooxygenase from the thermophilic bacterium Thermobifida fusca, exhibits a two-domain architecture resembling that of the disulfide oxidoreductases. The active site is located in a cleft at the domain interface. An arginine residue lays above the flavin ring in a position suited to stabilize the negatively charged flavin-peroxide and Criegee intermediates. This amino acid residue is predicted to exist in two positions; the "IN" position found in the crystal structure and an "OUT" position that allows NADPH to approach the flavin to reduce the cofactor. Domain rotations are proposed to bring about the conformational changes involved in catalysis. The structural studies highlight the functional complexity of this class of flavoenzymes, which coordinate the binding of three substrates (molecular oxygen, NADPH, and phenylacetone) in proximity of the flavin cofactor with formation of two distinct catalytic intermediates.
| S-EPMC516541 | biostudies-literature
Project description:Pyrroloxyls have been reported to exhibit very narrow EPR spectral lines, essential for in vivo imaging. En route to pyrroloxyls, we observed an unexpected Baeyer-Villiger rearrangement, leading to loss of aromaticity and formation of a 4,5-dihydro-1H-ketopyrrole.
| S-EPMC4041875 | biostudies-literature
Project description:Baeyer-Villiger monooxygenases (BVMOs) are biocatalysts that convert ketones to esters. Due to their high regio-, stereo- and enantioselectivity and ability to catalyse these reactions under mild conditions, they have gained interest as alternatives to chemical Baeyer-Villiger catalysts. Despite their widespread occurrence within the fungal kingdom, most of the currently characterized BVMOs are from bacterial origin. Here we report the catalytic and structural characterization of BVMOAFL838 from Aspergillus flavus. BVMOAFL838 converts linear and aryl ketones with high regioselectivity. Steady-state kinetics revealed BVMOAFL838 to show significant substrate inhibition with phenylacetone, which was more pronounced at low pH, enzyme and buffer concentrations. Para substitutions on the phenyl group significantly improved substrate affinity and increased turnover frequencies. Steady-state kinetics revealed BVMOAFL838 to preferentially oxidize aliphatic ketones and aryl ketones when the phenyl group are separated by at least two carbons from the carbonyl group. The X-ray crystal structure, the first of a fungal BVMO, was determined at 1.9 Å and revealed the typical overall fold seen in type I bacterial BVMOs. The active site Arg and Asp are conserved, with the Arg found in the "in" position. Similar to phenylacetone monooxygenase (PAMO), a two residue insert relative to cyclohexanone monooxygenase (CHMO) forms a bulge within the active site. Approximately half of the "variable" loop is folded into a short ?-helix and covers part of the active site entry channel in the non-NADPH bound structure. This study adds to the current efforts to rationalize the substrate scope of BVMOs through comparative catalytic and structural investigation of different BVMOs.
| S-EPMC4966971 | biostudies-literature