Diastereocontrolled synthesis of 6-hydroxy-1,3-dimethyl-5-(R*,R*-4-phenyl-1,2,3,4-tetrahydro-1H-β-carbolin-1-yl)-1H-pyrimidine-2,4-dione

While continuing work on synthesis and study of novel β-carboline systems [1, 2], we obtained 4-phenyl-3,4-dihydro-β-carboline (2) (a representative of the previously undescribed group of 4-aryl-substituted 3,4-dihydro-β-carbolines) by formylation of β-phenyltryptamine (1) followed by cyclization under Bischler– Napieralski reaction conditions. In contrast to known derivatives of this series, which are readily formed when the corresponding N-acyltryptamines are treated with phosphorus oxychloride [3], synthesis of compound 2 required considerably more vigorous conditions and was accompanied by secondary processes; the overall yield was only 20%. Since the diastereoselectivity is determined by either stereoelectronic factors or by steric factors [4], we hypothesized that if we used compound 2 in a Michael reaction and we used 1,3-dimethylbarbituric acid as the second component, then the reaction products would consist of two diastereomers with predominance of the R*,R*-isomer 3: