用两种可回收辛可尼定季铵盐催化剂催化合成L-苯丙氨酸

Preparation of L-phenylalanine with two newly-synthesized recoverable cinchonidine quaternary ammonium salt catalysts

目的:用2种新型辛可尼定季铵盐手性催化剂不对称催化合成L-苯丙氨酸(L-phe).方法:以辛可尼定,1-氯甲基苯并三唑或2-氯甲基苯并咪唑为原料,在甲苯中回流3h后过滤,得2种新型辛可尼定衍生物季铵盐手性催化剂.将该类催化剂用于催化N-二苯甲酮亚胺甘氨酸叔丁酯的不对称烷基化反应,得(S)-α-苄基二苯甲酮亚胺甘氨酸叔丁酯;再经过水解等步骤,得L-phe.体系中加入乙醚,过滤,使2种催化剂得到回收.结果:合成的2种新型辛可尼定季铵盐手性催化剂的化学产率分别达到90%和81%.(S)-α-苄基二苯甲酮亚胺甘氨酸叔丁酯的化学产率为75%～91%,对映体过量值为90%ee～99%ee,合成L-phe的总产率为41%～53%,2种催化剂的回收率为75%～80%.结论:2种辛可尼定季铵盐催化剂可催化N-二苯甲酮亚胺甘氨酸叔丁酯的不对称烷基化反应,并高产率地合成L-phe.手性催化剂可以回收.

AIM： To synthesize two novel cinchonidine quaternary ammonium salt chiral catalysts and to apply them in the preparation of L-phenylalanine （L-phe）. METHODS： Two new chiral quaternary salts were prepared from cinchona alkaloids and 2-chloromethyl benzimidazole or 1-chloromethyl benzotriazole. The chiral phase transfer catalysts were tested in enantioseleetive alkylation of N-（diphenylmethylene） glycine t-butyl ester to synthesize（S）-α-benzyl-N-（diphenylmethylene） glycine t-butyl ester, and L-phe was then obtained with hydrolysis. After reaction, the chiral phase transfer catalysts were recovered with the help of diethyl ether. RESULTS ： The yields of the chiral phase transfer catalysts were 90% and 81%. The yields and enantiomeric excess values of （S）-α-benzyl-N-（diphenylmethylene） glycine t-butyl ester were respectively 75%-91% and 90%-99% , and the total yields of L-phenylalanine was 41%-53%. The recovery rates of the catalysts were 75%-80%. CONCLUSION： Two novel cinchonidine quaternary ammonium salt catalysts are used in the asymmetric alkylation of N-（ diphenylmethylene ） glycine t-butyl ester and are recovered and reused. L-phenylalanine is prepared after the hydrolysis of （S）-α-benzyl-N-（ diphenylmethylene ） glycine t-butyl ester.