RESUMEN
Photocatalysis offers tremendous opportunities for enzymes to access new functions. Herein, we described a redox-neutral photocatalysis/enzymatic catalysis system for the asymmetric synthesis of chiral 1,2-amino alcohols via decarboxylative radical C-C coupling of N-arylglycines and aldehydes by combining an organic photocatalyst, eosin Y, and carbonyl reductase RasADH. Notably, this protocol avoids using any sacrificial reductants. A possible reaction mechanism proposed is that the transformation proceeds through sequential photoinduced decarboxylative radical addition to an aldehyde and a photoenzymatic deracemization pathway. This redox-neutral photoredox/enzymatic strategy is promising not only for effective synthesis of a series of chiral amino alcohols in a green and sustainable manner but also for the design of other novel C-C radical coupling transformations for the synthesis of bioactive molecules.
RESUMEN
2,2-Disubstituted-3-hydroxycyclopentanones are important chiral intermediates for natural products and pharmaceuticals. Through semirational engineering of a thermostable carbonyl reductase CBCR from Cupriavidus sp. BIS7, a mutant L91C/F93I was obtained. Mutant L91C/F93I showed 4- to 36-fold enhanced activities toward 2-methyl-2-benzyl-1,3-cyclopentanedione and its analogues, affording the (2R,3R)-stereoisomers with >99% ee and >99% de. Enzyme-substrate docking studies were performed to reveal the molecular basis for the activity and stereoselectivity improvements.
Asunto(s)
Oxidorreductasas de Alcohol , EstereoisomerismoRESUMEN
(S)-3-Cyclopentyl-3-hydroxypropanenitrile is the key precursor for the synthesis of ruxolitinib. The bioreduction of 3-cyclopentyl-3-ketopropanenitrile (1 a) offers an attractive method to access this important compound. A carbonyl reductase (PhADH) from Paraburkholderia hospita catalyzed the reduction of 1 a giving the (S)-alcohol (1 b) with 85 % ee. Rational engineering of PhADH resulted in a double mutant H93C/A139L, which enhanced the enantioselectivity from 85 % to >98 %, as well as a 6.3-fold improvement in the specific activity. The bioreduction of 1 a was performed at 200â g/L (1.5â M) substrate concentration, leading to isolation of (S)-1 b in 91 % yield. Similarly, using this mutant enzyme, 3-cyclohexyl-3-ketopropanenitrile (2 a) and 3-phenyl-3-ketopropanenitrile (3 a) were reduced at high concentration affording the corresponding alcohols in >99 % ee, and 90 % and 92 % yield, respectively. The results showed that the variant H93C/A139L was a powerful biocatalyst for reduction of ß-substituted-ß-ketonitriles.
Asunto(s)
Oxidorreductasas de Alcohol , Nitrilos , Oxidorreductasas de Alcohol/química , Etanol , Pirazoles , Pirimidinas , EstereoisomerismoRESUMEN
A series of 2,2-disubstituted trans,cis-cyclopentane-1,3-diols were synthesized in >99% dr through enzymatic reduction of enantiopure 2,2-disubstituted 3-hydroxycyclopentane-1-ones, which were prepared by highly stereoselective enzymatic reduction of the corresponding cyclodiketones. For 2-benzyl-2-methyl-3-oxocyclopentyl acetate, acetylation of the hydroxyl group significantly affected the reduction stereoselectivity, giving trans,cis-, trans,trans-, and cis,cis-2-benzyl-2-methyl-cyclopentane-1,3-diols in stereomerically pure form. This efficient and environmentally friendly method provides a practical approach to the synthesis of these chiral building blocks in single stereoisomeric form, demonstrating the power of biocatalysis in the concise chirality construction of complex chiral molecules.
RESUMEN
PURPOSE: To evaluate the stability of the miniscrew on different loading time as orthodontic anchorage. METHODS: 2 healthy adult male Beagle dogs were used in this study. 48 mini-implants were implanted into the maxilla and mandible of the dogs. The miniscrews were divided into 8 different groups,1 group was loaded 0g as control group and the others were loaded 200g forces as experimental groups. 200g forces were loaded on the corresponding mini-implant anchorages immediately after implantation and at the time of 1w,2w,3w,4w,5w and 6w after implantation. The dogs were sacrificed at 12w after implantation. Histological progresses of implant-bone interfaces was examined with light microscope. Blue deposition and contact ratio were calculated and analyzed using SPSS13.0 software package. RESULTS: Fibrous and osseous-integration was noted in the interface, there was no significant difference in bone deposition ratio and bone contact ratio. CONCLUSION: Different force loading time does not affect the stability of the mini-implant anchorage.