Proceedings book download - 5Z.com

Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Stereoselective Synthesis of Tetrahydro-β-carbolines viaPictet-Spengler ReactionSaeed Balalaie, Vahid DianatiPeptide Chemistry Research Center, K. N. Toosi University of Technology, Tehran,P.O. Box 15875-4416, Iran; balalaie@kntu.ac.irIntroductionThe tetrahydro-β-carboline ring system is present in numerous biologically active indolealkaloids as well as synthetic compounds.The Pictet-Spengler reaction is a powerful way ofaccessing tetrahydro-β-carbolines by the condensation of tryptamine derivatives andaldehyde through acid catalysis reaction conditions.The stereoselective synthesis of this new ring is an interesting subject for organicchemists. It was shown that the stereochemistry of the final product could affect thebiological activity of the carboline structure. Bailey, et al. found that the existence of achiral center could affect the stereoselectivity of the desired β-carboline structure [1]. Inthis regards, tryptophan is an interesting starting material, It was reported that tryptophanallyl esters reacted with benzaldehydes to give >95:5 cis:trans selectivity. It seems that theexistence of a chiral center in the structure of starting material has an effective influence onthe stereoselectivity of the products [2]. In continuation of our research work to find noveltandem reactions with ability of post-transformation, we wish to report herein stereoselectivesynthesis of tetrahydro-β-carboline containing propargyl moiety.Results and DiscussionIn this research, reaction of propargyl ester of tryptophan and its reaction with aromaticaldehydes in the presence of TFA was investigated. The desired β-carboline productshowed cis selectivity and the sole product was obtained as the cis isomer (Scheme 1).NHO+ ArCHONH 21 2Scheme 1. Synthesis of tetrahydro-β-carbolines.OTFACH 2Cl 2, 0°CMeanwhile, the starting material was synthesized according to this reaction sequence:1) formation of ester group using TBTU as coupling reagent, 2) Fmoc deprotection, 3) Bocdeprotection (Scheme 2).NHOONHAr 3NBocOOHNHFmoc1) 2-propyn-1-ol, TBTU,HOBt, DIEA, DMF2)HNEt 2 ,MeCN3)80%TFANHONH 2OScheme 2. Synthetic pathway to achieve starting material.For investigation of diversity and scope of reaction, different aromatic aldehydes whichcontained electron-donating or electron-withdrawing groups were selected. We chosepropargyl moiety to be able to carry out the click chemistry to form additional triazole ring.The results of the synthesis of desired tetrahydro-β-carbolines with cis-selectivity aresummarized in Table 1.92