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

Abstract

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 BischlerNapieralski 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:

Design and synthesis of Pictet–Spengler condensation products that exhibit oncogenic-RAS synthetic lethality and induce non-apoptotic cell death

“…18 Krasnov and coworkers reported a possible rearrangement (in the presence of proton source) between the 1, 2, 3, 4-tetrahydro-β-carboline and barbituric acid moieties, accompanied by opening of the tetrahydropyridine ring. 20 Thus, new analogs with a carbon spacer between the tetrahydro-β-carboline and the barbituric acid moieties were designed in order to avoid this rearrangement. The synthesis of tetrahydro-β-carbolines 15 and 17 is shown in Scheme 2.…”