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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Synthesis of Peptidomimetics by the Pictet-Spengler ReactionMarta Slupska 1 , Karolina Pulka 1 , Malgorzata Przygodzka 1 , andAleksandra Misicka 1,21 Faculty of Chemistry, Warsaw University, Warsaw, 02-093, Poland; 2 Medical ResearchCenter, Polish Academy of Science, Warsaw, 02-106, PolandIntroductionTryptophan is often a key pharmacophore which determines the affinity of peptide ligandsfor their receptors. Therefore cyclic analogues of tryptophan which introduce localconstraints, reduce the flexibility of the peptide chain and stabilize the bioactiveconformation are valuable tool in peptidomimetic research. The Pictet-Spengler [1] reactionhas been one of the possibilities to prepare analogues containing 1,2,3,4-tetrahydro-βcarbolineskeleton which introduce local constraints and reduce the flexibility of the indolemoiety of tryptophan. The heterocyclic skeleton of 1,2,3,4-tetrahydro-β-carbolinespossesses multiple sites for functionalization, therefore it is an ideal choice for the designpotent and selective ligands to biological target receptors. The use of chiral carbonylcomponents (e.g. α-aminoaldehydes) in Pictet-Spengler reaction influence the configurationof the newly created in this reaction stereogenic center [2].We now report the diastereoselectivity studies of Pictet-Spengler condensation ofL- and D-α-aminoaldehydes as carbonyl components with N-terminal α-Trp, β 2 - or β 3 -homo-Trp dipeptides as arylethylamine substrates.Results and DiscussionThe synthesis of L-β 3 -homo-tryptophan was accomplished by Arndt-Eistert homologationof L-α-tryptophan [3]. Optically active L-β 2 -homo-tryptophan was synthesized with the useof (+)-2,10-camphorsultam as chiral auxiliary [4].The Pictet-Spengler cyclizations of different tryptophan derivatives with L- and D-αaminoaldehydeswere performed in the presence of TFA and at low temperature (-40°C) toavoid racemization of chiral aminoaldehydes (Figure 1).Fig. 1. a) Synthesis of tetrahydro-β-carbolines, b) 2D NMR ROESY spectra of cis/transproducts of Pictet-Spengler condensations of L-α-Trp-OCH 3 with Cbz-L-Ala-H.242