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

Satoshi Hibino, Takeshi Kuwada, Miyako Fukui, Tominari Choshi, Junko Nobuhiro, Toshiyuki Hata, Yukio Ono
2003 19th International Congress on Heterocyclic Chemistry  
The cytocidal b-carboline alkaloids, oxopropalines A (1), B (2), and D (3), were isolated from Streptomyces sp. G324 together with two related oxopropalines E and G, which produce lavendamycin, by Abe and co-workers in 1993 (Chart 1). 1,2) This new b-carboline alkaloid possessing an acyl group and a methyl group at the 1-and 4-positions exhibits cytocidal activity. Oxopropalines A (1) and B (2) have been converted into oxopropaline D (3) by acidic methanolysis. Natural oxopropaline D (3) has
more » ... itive rotation, but the absolute stereochemistry of both 3a and 3b has not been determined yet (Chart 2). Recently we reported the total syntheses of (ϩ)-and (Ϫ)-oxopropaline D (3) by the construction of a new b-carboline framework based on a thermal electrocyclic reaction of a 1-azahexatriene system involving an indole 2,3bond, followed by enantioselective 1,2-dihydroxylation. 3) We described in the report 3) that absolute configurations of (ϩ)-3 and (Ϫ)-3 are presumed to have S and R, respectively, in accordance with the Sharpless rule. 4) In the present study, we describe here the determination of the absolute configuration of (ϩ)-oxopropaline D (3). We initially estimated whether the (R)-oxopropaline D refers to either the plus or minus sign of a specific optical rotation calculated by an ab initio MO method that was previously reported by the Kondru group. 5) Based on the absolute configuration estimated as R, an asymmetric synthesis of (R)-oxopropaline D acetonide (4a) was carried out in order to compare the results with those of previously synthesized (ϩ)-oxopropaline D acetonide (4). 3) 20 The specific optical rotations of (R)-oxopropaline D calculated by two ab initio MO methods were ؉52؎31°a nd ؉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-b b-carboline with (R)-glyceraldehyde acetonide followed by oxidation with MnO 2 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; (ϩ)-oxopropaline D; specific optical rotation; ab initio MO method; asymmetric synthesis; (R)-(ϩ)-oxopropaline D acetonide Chart 1 Chart 2
doi:10.1016/b978-0-08-044304-1.50164-7 fatcat:bxainjyuozbf3fcobkujgdnnm4