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Synthesis of B-carboline Derivatives
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1  Chemistry Centre, School of Sciences, University of Minho, Braga, Portugal

Abstract: b-Carboline (BC) alkaloids represent a number of natural and synthetic compounds, which are associated with a vast spectrum of pharmacological properties.1 The Pictet-Spengler condensation is commonly used to synthesize tetrahydro-b-carbolines (THC). Some groups2 describe a sequence of Pictet-Spengler condensation followed by oxidation, without the isolation of the intermediate THC, to prepare the BC. Using the above sequence several BC were obtained in medium yields. The synthesis started from tryptophan (Trp), tryptophan methyl ester (TrpMe), and 2-amino-3-(1H-indol-3-yl)-propionic acid prop-2-ynyl ester and used 3,4-dimethoxy benzaldehyde (Dmb), or ethanal, followed by oxidation with KMnO4. From Trp, and Dmb the decarboxylated BC was obtained. From TrpMe and Dmb, the methyl ester of a BC was formed. A similar sequence with ethanal, gave an ester that was hydrolysed to theacid, which reacted with a glucosylamine under peptide conditions giving the amide, in low yield. From Boc-Trp the alkynyl derivative was prepared and the Pictet-Spengler reaction with ethanal gave the BC alkynyl ester. This was used for the click reaction3 with an azide, produced in situ from treatment of a-acetobromoglucose with sodium azide. The final compound was obtained as an oil in good yield. Thanks to FCT, Portugal for financial support to the NMR portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho) and to FCT and FEDER -COMPETE-QREN-EU for financial support to the Research Centre, CQ/UM [PEst-C/QUI/UI0686/2011 (FCOMP-01-0124-FEDER-022716)] 1. R, Cao, et al, Curr Med Chem. 2007. 14, 479-500 2. B. Wu, et al, Eur. J. Med. Chem.. 2009. 44, 533-540 3. M. Silva, J. C.O. Gonçalves, A. M.F. Oliveira-Campos, L. M. Rodrigues, A. P. Esteves, Synth. Commun. DOI:10.1080/00397911.2011.637655
Keywords: beta-carbolines, click reaction, alkynyl ester, glucopyranose