A Chiral Synthesis of Four Stereoisomers of 1, 3-Dimethyl-1, 2, 3, 4-tetrahydroisoquinoline, an Inducer of Parkinson-like Syndrome

Abstract

Four stereoisomers of 1, 3-dimethyl-1, 2, 3, 4-tetrahydroisoquinoline, an inducer of Parkinson-like syndrome, were synthesized by applying a new method of 1, 2, 3, 4-tetrahydroisoquinoline (TIQ) synthesis utilizing the Pummerer reaction as a key step. The chiral centers at C-1 and C-3 were constructed by two routes starting from alaninol (3) and 1-phenylethylamine (4) as a chiral source. Enantiomerically pure 1, 3-dimethyl-TIQs (1R, 3S)-(1), (1S, 3R)-(ent-1), (1S, 3S)-(2), and (1R, 3R)-(ent-2) were prepared in a stereochemically unambiguous manner from 3 in 11 steps (route I) and from 4 in 6 steps (route II). The conformations of tetrahydroisoquinoline ring in 1-methyl, 3-methyl, and 1, 3-dimethyl-TIQs were discussed on the basis of their CD, ¹H-NMR spectra, and steric energies.