Synthesis and Technology Optimization of Dapoxetine Hydrochloride / 中国药房

OBJECTIVE：To optimize the synthesis process of dapoxetine hydrochloride. METHODS ：By chiral synthesis ， asymmetric reduction was carried out by using 3-chlorophenylacetone as raw material ，（1S，2R）-（-）-1-amino-2-indanol as catalyst，and borane- N，N-diethylaniline （DEANB） as reducing agent. Then ，it was reacted with α-naphthol etherification， sulfonation，dimethylamine substitution ，and HCl salt formation reaction to obtain the final products. The products were characterized by NMR and MS. The synthesis reaction of intermediate Ⅰ，intermediate Ⅱ，intermediate Ⅲ and the final product were optimized. RESULTS ：The final product was dapoxetine hydrochloride with purity of 99.8％ and yield of 58.9％. Compared with traditional splitting technology ，the chiral synthesis technology of this study did not need splitting ，and the yield of the technology was significantly higher than that of splitting technology reported in literature （31.9％）. The optimized technology reduced the generation of impurities and improved the product quality. CONCLUSIONS ：The improved technology has milder reaction conditions ，shorter synthesis route and higher yield.

Process improvement on the synthesis of atomoxetine / 中国药科大学学报

@#Atomoxetine is a highly selective norepinephrine reuptake inhibitor. Based on the analysis of the literature methods, the synthesis process of atomoxetine was improved. Using 3-chloropropiophenone-1 as the raw material, optically pure target product was obtained by asymmetric reduction, Mitsunobu reaction and condensation reaction in three steps, with a total yield of 26%. The third-step methylation sealing operation was changed to the reaction under normal pressure, which increased the feasibility of industrialization. The improved process operation was simplified and the reaction conditions were mild, which would provide a new method for the preparation of atomoxetine.

Cloning and Expression of Gene Encoding (R)-specific Carbonyl Reductase from Candida parapsilosis CCTCC M203011 in Escherichia coli / 微生物学通报

The gene which encodes (R)-specific carbonyl reductase(rCR) from Candida parapsilosis CCTCC M203011 was cloned.The cloned sequence includes an open reading frame (ORF) consisting of 1011bp, encoding a protein of 336 amino acids, with a molecular weight of 35.9 kD.The nucleotide sequence showed 99% similarity to those of the other members of the alcohol dehydrogenase superfamily.A recombinant Escherichia coli JM109 strain harboring the expression plasmid, produced (R)-1-phenyl-1,2-ethanediol(100%e.e,80.4%yield) from ?-hydroxyacetophenone without any additive to regenerate NAD~ + from NADH.