159690-58-1

Upstream product

• 946-33-8 (R)-2-benzylcyclohexanone 
• 946-33-8 2-benzylcyclohexan-1-one 

Downstream Products

• 159690-66-1 (R)-10-methyl-1-(benzyl)undecyl acetate 
• 159690-59-2 methyl (R)-6-hydroxy-7-phenylheptanoate 
• 159690-73-0 (R)-1-phenyloctan-2-yl acetate 
• 159690-65-0 (R)-11-Methyl-1-phenyl-dodecan-2-ol 
• 159690-72-9 (R)-1-phenyl-2-octanol 
• 76904-91-1 (R)-3-((R)-3,3,3-Trifluoro-2-methoxy-2-phenyl-propionyloxy)-nonanoic acid methyl ester 
• 121541-65-9 (R)-(-)-1,3-nonandiol 1 

Relevant academic research and scientific papers

Comparison of microbiologically and enzymatically mediated Baeyer-Villiger oxidations: Synthesis of optically active caprolactones

Optically active α-substituted caprolactones (7-substituted oxepan-2-ones) were obtained by biocatalysed Baeyer-Villiger oxidations of various α-substituted cyclohexanones using either whole-cells of Acinetobacter TD63 or a purified cyclohexanone monooxyg

Investigation of a New Type I Baeyer–Villiger Monooxygenase from Amycolatopsis thermoflava Revealed High Thermodynamic but Limited Kinetic Stability

Baeyer–Villiger monooxygenases (BVMOs) are remarkable biocatalysts, but, due to their low stability, their application in industry is hampered. Thus, there is a high demand to expand on the diversity and increase the stability of this class of enzyme. Sta

Induced allostery in the directed evolution of an enantioselective Baeyer-Villiger monooxygenase

The molecular basis of allosteric effects, known to be caused by an effector docking to an enzyme at a site distal from the binding pocket, has been studied recently by applying directed evolution. Here, we utilize laboratory evolution in a different way, namely to induce allostery by introducing appropriate distal mutations that cause domain movements with concomitant reshaping of the binding pocket in the absence of an effector. To test this concept, the thermostable Baeyer-Villiger monooxygenase, phenylacetone monooxygenase (PAMO), was chosen as the enzyme to be employed in asymmetric Baeyer-Villiger reactions of substrates that are not accepted by the wild type. By using the known X-ray structure of PAMO, a decision was made regarding an appropriate site at which saturation mutagenesis is most likely to generate mutants capable of inducing allostery without any effector compound being present. After screening only 400 transformants, a double mutant was discovered that catalyzes the asymmetric oxidative kinetic resolution of a set of structurally different 2-substituted cyclohexanone derivatives as well as the desymmetrization of three different 4-substituted cyclohexanones, all with high enantioselectivity. Molecular dynamics (MD) simulations and covariance maps unveiled the origin of increased substrate scope as being due to allostery. Large domain movements occur that expose and reshape the binding pocket. This type of focused library production, aimed at inducing significant allosteric effects, is a viable alternative to traditional approaches to designed directed evolution that address the binding site directly.

Laboratory evolution of robust and enantioselective Baeyer-Villiger monooxygenases for asymmetric catalysis

The Baeyer-Villiger Monooxygenase, Phenylacetone Monooxygenase (PAMO), recently discovered by Fraaije, Janssen, and co-workers, is unusually thermostable, which makes it a promising candidate for catalyzing enantioselective Baeyer-Villiger reactions in organic chemistry. Unfortunately, however, its substrate scope is very limited, reasonable reaction rates being observed essentially only with phenylacetone and similar linear phenyl-substituted analogs. Previous protein engineering attempts to broaden the range of substrate acceptance and to control enantioselectivity have been met with limited success, including rational design and directed evolution based on saturation mutagenesis with formation of focused mutant libraries, which may have to do with complex domain movements. In the present study, a new approach to laboratory evolution is described which has led to mutants showing unusually high activity and enantioselectivity in the oxidative kinetic resolution of a variety of 2-aryl and 2-alkylcyclohexanones which are not accepted by the wild-type (WT) PAMO and of a structurally very different bicyclic ketone. The new strategy exploits bioinformatics data derived from sequence alignment of eight different Baeyer-Villiger Monooxygenases, which in conjunction with the known X-ray structure of PAMO and induced fit docking suggests potential randomization sites, different from all previous approaches to focused library generation. Sites harboring highly conserved proline in a loop of the WT are targeted. The most active and enantioselective mutants retain the high thermostability of the parent WT PAMO. The success of the "proline" hypothesis in the present system calls for further testing in future laboratory evolution studies.

A light-driven stereoselective biocatalytic oxidation

Let the sunshine in: Light can be used to drive enantioselective Baeyer-Villiger oxidations of cyclic ketones catalyzed by a flavin-dependent enzyme. Photochemical reduction of the flavin using ethylenediaminetetraacetate (EDTA) as the sacrificial electron donor closes the catalytic cycle, thus providing a means to directly regenerate reduced flavin cofactors without the need for costly nicotinamide cofactors as electron donors. (Chemical Equation Presented).

Converting phenylacetone monooxygenase into phenylcyclohexanone monooxygenase by rational design: Towards practical Baeyer-Villiger monooxygenases

A homology model of the most frequently used, but thermally somewhat labile, Baeyer-Villiger monooxygenase, cyclohexanone monooxygenase (CHMO) has been derived on the basis of the recently published crystal structure of the thermally stable phenylacetone monooxygenase (PAMO). This has led to the identification of a structural element crucial for substrate acceptance and stereoselectivity, namely an arginine-interacting loop near the active site. A bulge in this loop occurring in PAMO (but not in CHMO) has been eliminated by mutation, enhancing the range of substrate acceptance and enantioselectivity of Baeyer-Villiger reactions while maintaining high thermal stability.

Application of Microbial Enantiofacially Selective Hydrolysis in Natural Product Synthesis

Pichia farinosa IAM 4682 mediated enantiofacially selective hydrolysis worked efficiently (65-70percent yield) on the interface-bioreactor in a reproducible manner, which established the product, (R)-2-benzylcyclohexanone (84-87percent e.e.), to be the starting material for the synthesis of optically active natural products.Methyl (R)-3-hydroxy-12-methyltridecanoate, a constituent of lipopolysaccharide, and (R)-1,3-nonanediol, a secretion of cucumber fly, were synthesized via this common intermediate, of which the optically active secondary alcohol moiety was derived from the above chiral ketone by Baeyer-Villiger oxidation.Final products were enantiomerically enriched to 94-95percent e.e., by the lipase-mediated enantioselective transesterification, which could remove the minor enantiomer as the corresponding acetate.