(S)-2-氨基-1,1-二苯基-1-丙醇的合成和外消旋Droxidopa前体的拆分

(S)-2-氨基-1,1-二苯基-1-丙醇是一种合成多种手性助剂的重要中间体,也用于外消旋屈昔多巴前体化合物的拆分。从价廉易得的L-丙氨酸出发,通过四步反应制得,总收率55.6%L-丙氨酸经甲酯化,苄氧羰基保护制得的L-2-苄羰基氨基丙酸甲酯与苯基溴化镁反应制得(S)-2-苄氧羰基氨基-1,1-二苯基-1-丙醇。是在5%Pd/C催化加氢下脱除苄氧羰基得到标题化合物。该制备方法涉及的中间体及目标化合物易于纯化,总收率高且重现性好。我们用制得的氨基醇能成功地拆分外消旋苏式屈昔多巴前体化合物3-3,4-二苄氧苯基)-N-苄氧羰基丙氨酸。

Synthesis of (S) - - 2 - amino - 1,1 - diphenyl - 1 - propanol, a resolving reagent to racemic droxidopa Precursor

(S)--2-Amino-1,1-diphenyl-1-propanol(3),an important compound for many chiral catalysts and a good re-solving reagent to racemic Droxidopa precursor was prepared by 4 steps from L-alanine with total yield of 55.6%.L-2-Benzy-loxycarbonylamino-propionic acid methyl ester(1),which was obtained from L-alaninge by methy lation and benzyloxycarbonyla-tion,reacted with PhMgBr to give(S)-2-Benzyloxycarbonylamino-1,1-diphenyl-1-propanol(2).2 hydrogenolysized withH2catalyzed by 5%Pd/C to give target compond 3.3 was successfully applied to resolve rac-threo3-(3,4-dibenzyloxyphenyl)-N-carbobenzoxyserine(4)which is Droxidopa(5)precursor.This new method has good reproducibility and simple purificationprocess as well as relatively high total yield.