Study On The Deracemization Of Antiviral Agents Intermediate By Microbial Processes

(1R,4S)-2-azabicyclo[2.2.1]-hept-5-en-3-one [(-)-γ-Lactam] is one of the key starting materials for the synthesis of two powerful antiviral agents (-)-cabovir and (-)-abacavir. The production of (-)-γ-Lactam using enzymatic resolution of racemic γ-lactam was studied in the paper.20strains capable of producing lactamase were screened from soil samples collected in several areas throughout Beijing; employed N-actylphenylalanine as the sole carbon source. The chiral HPLC analysis results showed that strain L29-9was one of the best stains which can enantioselectively catalyze the hydrolysis of the racemic lactam to give its (-)-isomer enatiopure with high enantiomeric excess.Ferment conditions of strain L29-9, including carbon sources, nitrogen sources, pH, and culturing time, were optimized as following: citric acid2g/L, yeast extract5g/L, temperature30℃, pH7.0, culturing for40h. Biotransformation using whole cells of the strain was carried out at30℃for12h, giving (-)-γ-lactam with yield up to40%and ee99.5%.Extract genomic DNA from L29-9as template, and amplified by PCR.16sRNA sequence was determined by dideoxynucleotide termination method. The sequence compared with NCBI, shown that L29-9is Microbacterium hydrocarbonoxydans.