Resolution Of N-Acylalanines

N-Acylalanines belong to a series of syatemic fungicides with high biological activity and low mammal toxicity. They posses the natures of prevention and care of plant diseases caused by Pythium irregulars, Plasmopara viticola and Zoospores germination. The general structure of the N-Acylalanines as fungicides is following:N-C(C)-C in the molecular structure is the funficidally active radical. It has one chiral C and a pair of enantiomeric isomers. The activity of R-isomer is higher than that of S-isomer. N-(2,6-xylyl)-alanine is the most important intermediates of N-Acylalanines.Methyl N-(2, 6-xylyl)-alanine was prepared from -chloropropionic acid. The yields of the two reactions are 90% and 92%, respectively. The chemical purities of the product are more than 95%.Chiralreagents, such as S-(+)- - phenylethylamine, L-cinchonine , L-(+)-N, N-dimethyl-4-nitrophenyl- -hydrox-isobutylamine and R-(+)-4-chlorophenyl -isobutylamine were used for the resolution of methylN-(2, 6-xylyl)-alanine. Among those, S-(+)- -phenylethylamine gave the best one with the recovery of 92%. Optical isomers of N-(2,6-xylyl)-alanine were used for preparing their L-menthol ester, which could be resoluted and determined on an ordinary column by HPLC. The optical purity of R-(+)-N-(2, 6-xylyl)-alanine was more than 98%, that of S-(-)-isomer is 55.4%.Methyl N- (2,6-xylyl)-alanine is resoluted by Candida rugosa lipases (CRL).The reaction is optimized from pH, amounts of lipase, subsidiary, stirring speed of shaker bath and temperature. Under theconditions of pH 6. 4, amounts of lipase 250mg, PEG of 2g, the stirring speed 160 r.p. m and the temperature 35 C, the best results were obtained. Temperature and amounts of lipase were more important than the others. CRL was reacted much more quickly with methyl 5-N-(2, 6-xylyl)-alanate than that with R isomer. Thus, methyl R-N-(2, 6-xylyl)-alanate was given from reacted liquid, which was the intermediate with optical activity we need. Optical active N-acylalanines were prepared from methyl R-N-(2, 6-xylyl)-alanate. The convertion and enantiomeric excess was determined by HPLC.Compared with chemical resolution, which need four reactions, a number of solvents, the resolution by CRL can be finished with only one reaction, milder condition and less solvents.