The advance of ω-transaminase in chiral amine biosynthesis in China from the perspective of patents / 生物工程学报

ω-transaminases are able to catalyze the reversible transfer of amino groups between diverse amino compounds (such as amino acids, alkyl amines, aromatic amines) and carbonyl compounds (such as aldehydes, ketones, ketoacids). ω-transaminases exhibit great application prospects in the field of chiral amine biosynthesis because of their desirable properties, such as wide range of substrates, high stereoselectivity, and mild catalytic conditions. It is therefore important for China to develop efficient, specific, and environment-friendly chiral amine production technologies with independent intellectual property rights, which is of great significance for the development of pharmaceutical, pesticide, and material industries. This review systematically summarizes the Chinese patents regarding ω-transaminase filed by Chinese institutions in the recent decade. The development of ω-transaminase resource, enzymatic property improvement by protein engineering, application in chiral amine synthesis, and development of production technologies are elaborated. This review will shed light on further basic and application studies of ω-transaminase.

Chemistry of steroidal saponins as natural resource compounds / 中国药科大学学报

@#This article briefly summarizes our group′s systematic studies on the resource chemistry of steroidal sapogenins. Steroidal sapogenins are an important class of natural compounds, which could be utilized to synthesize various steroidal drugs. In order to achieve their efficient, clean and atom-economical utilization, our research group systematically investigated the oxidative degradation reaction of steroidal sapogenins. By employing 30% H2O2 as the oxidant, pseudo-sapogenins and sapogenins could be oxidized to the corresponding pregnenolone, pregnane-3β, 16, 20-triol, steroidal 22-lactone, as well as a series of bifunctional reagents with chiral methyl group. These oxidative degradation products have been applied to the synthesis of steroidal drugs, biologically active natural steroidal molecules and non-steroid functional chiral molecules. Furthermore, we explored the bromination-ring opening, amination-ring opening and bromolactonization reactions of the spiroketal moiety, which provides new strategies and methods in the utilization of their intact skeleton to the efficient syntheses of active components of traditional Chinese medicines with the cholesterol skeleton, as well as biologically active steroidal natural products.

An improved preparing process for rivastigmine / 中国药科大学学报

@#An improved manufacturing process for rivastigmine(1)was developed by performing the condensation reaction of m-hydroxyacetophenone(4)with N-ethyl-N-methyl carbamoyl chloride, then Corey-Bakshi-Shibata(CBS)chiral reduction to(R)-3-(1-hydroxyethyl)phenyl ethyl(methyl)carbamate(2)and then mesylation with methanesulfonyl chloride and nucleophilic substitution with dimethylamine, respectively. To be successful, a crucial reductive process in the conversion of ketone(3)to chiralalcohol(2)had to be correctly understood and optimized via orthogonal experiment. The whole improved process was convenient for operation and purification, with completion of the synthesis of rivastigmine and an overall yield of 88%.

Synthesis, XRD analysis and anti-tumor activity of novel compounds containing tetrahydronaphthalen-2-ol / 药学实践杂志

Objective To synthesize the enantiomers of ( E)-6-methoxy-1-(3,4,5-trimethoxybenzylidene )-1,2,3,4-tetra-hydronaphthalen-2-ol,determine their structures by XRD and evaluate their anti-tumor activity in vitro.Methods The target compounds were prepared from 2,6-Dimethoxybenzoyl chloride.The key intermediate,(E)-6-methoxy-1-(3,4,5-trimethoxybenzylidene)-1,2,3,4-tetrahydronaphthalen-2-one,was obtained through Cornforth reduction and Knoevenael reaction ,and the final R,S compounds were got by CBS asymmetric reduction .The structure of the target compounds were determined by XRD .The target compounds were rested by anti-tu-bulin and anti-tumor assay.Results The structure of the target compounds were determined by 1 H NMR,13 C NMR,MS,and XRD analy-sis.The yield of asymmetric reduction reaction was 90.3%,e.e.%was 99.04%,in vitro anti-tumor assay showed all of the S isomer had stronger anticancer activity than the R isomer ,especially on CCRF-CEM cell(IC50 =1 nmol/L),HCT-116 cell(IC50 =0.14μmol/L) and inhibition of tubulin polymerization ( IC50 =0.41μmol/L) .Conclusion The CBS asymmetric reduction was a good way to get high-yield and high optical purity compound .The S isomer with outstanding anticancer activity was worth further research .

Carboidratos como matéria-prima para a preparação de substratos quirais: aplicações em catálise enantiosseletiva e processos diastereosseletivos / Carbohydrates as starting materials for the preparation of chiral substrates: applications in enantioselective and diastereoselective processes

O presente trabalho descreve o uso de carboidratos como materiais de partida para a preparação de catalisadores quirais e também de substratos quirais. Primeiramente estudos envolvendo a aplicação de amino álcoois derivados de carboidratos na arilação assimétrica de aldeídos, usando ácidos arilborônicos como fontes de grupos arila transferíveis, revelaram que um ligante preparado a partir da D-xilose mostrou-se bastante eficiente e conduziu aos produtos em excelentes rendimentos e altos excessos enantioméricos. Posteriormente a arilação de aldeídos derivados de carboidratos é descrita. Em alguns casos diastereosseletividades maiores que 20:1 foram observadas e a metodologia foi aplicada a síntese total da 7-epi-goniofufurona e análogos

The work described herein is centered on the use of carbohydrates as starting materials for the synthesis of chiral ligands and chiral sugar-derivatives. Initially, chiral amino alcohols were studied as ligands for the asymmetric arylation of aldehydes using aryl boronic acids as the source of transferable aryl groups. We found that a chiral ligand derived from D-xylose was very efficient and the desired products were obtained in excellent yields and enantiomeric excesses. In addition, the arylation of sugar-based aldehydes was also studied. In many cases, excellent diastereoselectivities of >20:1 were achieved and the methodology was employed in the total synthesis of 7-epi-goniofufurone and analogues