First synthesis of (R)- and (S)-1,2,3,4-tetrahydroisoquinoline-3-phosphonic acid (TicP) using a pictet-spengler reaction

摘要

We report here a practical and efficient synthesis of diethyl 1,2,3,4-tetrahydroisoquinoline-3-phosphonate derivatives. The target compounds were prepared in good yield using a Pictet-Spengler reaction involving α-amino phosphonates that were easily obtained. We have paid special attention to the synthesis of (R)- and (S)-1,2,3,4-tetrahydroisoquinoline-3-phosphonic acid (Tic) 2a, a conformationally constrained analogue of phosphophenylalanine Phe. The procedure is based on the preparation of racemic phosphophenylalanine (Phe) diethyl ester followed by chiral chromatographic separation and subsequent Pictet-Spengler chemistry.