(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

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

(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。

（S） - -2 -Amino- 1,1 -diphenyl- 1 -propanol（3 ）, an important compound for many chiral catalysts and a good resolving reagent to racemic Droxidopa precursor was prepared hy 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 benzyloxycarbonylation, reacted with PhMgBr to give （S） - 2 - Benzyloxycarbonylamino - 1,1 - diphenyl - 1 - propanol （ 2 ）. 2 hydrogenolyaized with H2 catalyzed by 5% Pd/C to give target oompond 3.3 was successfully applied to resolve rac - threo 3 - （3,4 - dibenzyloxyphenyl） -N- carbobenzoxyserine（4）which is Droxidopa（5 ）precursor. This new method has good reproducibility and simple purification process as well as relatively high total yield.