A chiral synthesis of four stereoisomers of 1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline, an inducer of Parkinson-like syndrome.
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)-(2) [corrected], (1S,3R)-(ent-2) [corrected], (1S,3S)-(1) [corrected], and (1R,3R)-(ent-1) [corrected] 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.
Toda
J
J
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Matsumoto
S
S
Saitoh
T
T
Sano
T
T
D002851:Chromatography, High Pressure Liquid; D007546:Isoquinolines / Q000737:chemistry* / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C065331:1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline; C014843:1,2,3,4-tetrahydroisoquinoline