手性药物前体R(-)-扁桃酸的生物不对称合成

 目的研究生物不对称催化苯乙酮酸合成手性药物前体R(-)-扁桃酸。方法通过对本实验室保存的12株酵母菌进行初筛,获得对底物苯乙酮酸具有较高催化活性的菌株S.c.1,S.c.3和S.c.10。进一步对其进行紫外与微波诱变,得到R(-)-扁桃酸高产菌株S.c.10.2.8。结果在转化培养中,初始底物浓度为20mmol·L^-1,pH6.6,温度34℃,R(-)-扁桃酸得率85%,对映体过量值(e.e)>99%。结论生物转化法在生产手性药物前体R(-)-扁桃酸中前景广泛。

Study on Asymmetric Synthesis of Chiral Precursor R(-)-mandelic Acid

OBJECTIVE To study the synthesis of chiral precursor R(-)-mandelic acid obtained by asymmetric bioreduction of phenylglyoxylic acid.METHODS Saccharomyces cerevisiae strains S.c.1,S.c.3 and S.c.10 were selected as original strains for further higher production of chiral precursor R(-)-mandelic acid.The mutant strain S.c.10.2.8 possessing effective transforming ability and almost absolute enantioselectivity was obtained using ultraviolet and microwave mutagenesis.RESULTS Under the conditions of initial substrate concentration 20 mmol·L^-1,pH 6.6,temperature 34 ℃,the yield and the enantiomeric excesses of R(-)-mandelic acid were 85% and 99% respectively.CONCLUSION Biotransformaton is a potential alternative method to produce chiral precursor R(-)-mandelic acid.