Preparation of (R) and (S) alpha methyldopa from a chiral hydantoin containing the alpha phenylethyl group.
Chiral hydantoin (S)-1 was prepared in good yield from phenyl isocyanate and N-[(S)-alpha-phenylethyl]glycinate, (S)-3. Enolate (S)-1-Li was methylated in high yield and good diastereoselectivity. In contrast, a second alkylation reaction of methylated enolate (S)-4-Li proceeded with essentially no diastereoselectivity. Nevertheless, dialkylated hydantoins, (S,S)-7 and (S,R)-7, could be readily separated by flash chromatography and subsequent hydrolysis of either derivative afforded the desired (S)-L-alpha-methyldopa or (R)-D-alpha-methyldopa in good yield.
León-Romo
José Luis
JL
Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, D.F., México.
Virues
Claudia I
CI
Aviña
Judit
J
Regla
Ignacio
I
Juaristi
Eusebio
E
D000478:Alkylation; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry; D006827:Hydantoins / Q000737:chemistry*; D007202:Indicators and Reagents; D008750:Methyldopa / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
D000959:Antihypertensive Agents; D006827:Hydantoins; D007202:Indicators and Reagents; D008750:Methyldopa