title: Three-step synthesis of (R)- and (S)-thalidomides from ornithine.
abstract: Three-step synthesis of enantiomerically pure thalidomide is described. D-Ornithine (2) reacted with thionyl chloride in methanol followed by treatment with triethylamine to give the (R)-3-amino-piperidin-2-one hydrochloride (3) in good yield. Protection of amino moiety by the use of N-carboethoxyphtalimide in DMSO furnished (R)-N-phtaloylpiperidin-2-one (4) as colorless crystals. Finally, the oxidation using a catalytic amount of RuO2 in the presence of excess sodium metaperiodate in a two-phase system gave (R)-thalidomide (1) in good yield without racemization. (S)-Thalidomide (1) was also synthesized from L-ornithine (2) in good overall yield. Since all the intermediates to thalidomide are easily recrystallized, the present method can be performed on a large scale without purification by column chromatography.
authors.affiliation: Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Shibata