Chem. Pharm. Bull., 51(1),20-23, January 2003

Regular Articles

The Absolute Configuration of (+)-Oxopropaline D by Theoretical Calculation of Specific Rotation and Asymmetric Synthesis

Takeshi KUWADA,^b Miyako FUKUI,^a Toshiyuki HATA,^a Tominari CHOSHI,^a Junko NOBUHIRO,^a Yukio ONO,^a and Satoshi HIBINO^*,a

^a Graduate School of Pharmacy and Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University; Fukuyama, Hiroshima 729-0292, Japan: and ^b Process Chemistry Laboratory, Medicinal Research Laboratory, Taisho Pharmaceutical Co. Ltd.; 1-403 Yoshino-cho, Saitama, Saitama 330-8530, Japan. * To whom correspondence should be addressed. e-mail: hibino@fupharm.fukuyama-u.ac.jp

The specific optical rotations of (R)-oxopropaline D calculated by two ab initio MO methods were +52±31° and +61±29°, respectively, and (+)-oxopropaline D (3) was presumed to have an R-configuration. On the basis of this theoretical result, the reaction of 1-litio-β-carboline with (R)-glyceraldehyde acetonide followed by oxidation with MnO₂ gave (R)-oxopropaline D acetonide (4a), which was consistent with the previously synthesized (+)-oxopropaline D acetonide (4) in all respects. From the results of theoretical calculations and the experimental synthesis, we determined that natural (+)-oxopropaline D (3) has an R-configuration.

Key words absolute configuration; (+)-oxopropaline D; specific optical rotation; ab initio MO method; asymmetric synthesis; (R)-(+)-oxopropaline D acetonide