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Table 1. Synthesis of tetrahydro-β-carbolines via Pictet-Spengler ReactionAldehydeCHOProductNHOONHYield(%)AldehydeCHOProductYield(%)N73 H62NHOOCHONHOONHCHONH52NH67OOClCHONHClOONHNO 2CHOO 2NOON66 H64NHOMeOMeNO 2NO 2The distinguished peak for the stereo selective synthesis of product in 1 H- and 13 C-NMRspectra are related to the chemical shifts of H-1 and H-3 protons.O52.3OMeNHNH54.9O56.9OMeNHN 58.7HO56.8ONHNH58.6O57.3ONHNH59.1Scheme 3. Comparison of chemical shifts of the products with the synthetic cis- tetrahydroβ-carbolineisomers.The value of coupling constants and also chemical shifts could confirm the cis isomer asthe final product.The yields of products were between 52-73%. The products have thesuitable functional groups for carrying out the further reactions.In summary, we have found that the Pictet-Spengler reaction of tryptophan propargylesters with aromatic and heteroaromatic aldehydes generates cis-tetrahydro-β-carbolineswith stereoselectivity.This reaction tolerates all substituted phenyl derivatives that we triedfor aldehyde which means that this should be adaptable to a wide range of targets ofmedicinal synthetic interest.References1. Alberch, L., Bailey, P.D., Clingan, P.D., Mills, T.J., Price, R., Pritchard, R.G. Eur. J. Org. Chem.1887 (2004).2. Bailey, P.D., Beard, M.A., Phillips T.R. Tetahedron Lett. 50, 3645-3648 (2009).3. Sewgobind, N.V., Wanner, M.J., Ingemann, S., de Gelder, R., van Maarseveen, J.H., Hiemstra, H. J.Org. Chem. 73, 6405-6408 (2008).93
Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Synthesis of Aza-β 3 -Homoserine, Incorporation of This NewAza-β 3 -Amino Acid Into 26RFa (20-26) and Microwave-AssistedDeprotection of Its Side ChainOlivier Tasseau 1 , Patrick Bauchat 1 , Cindy Neveu 2 , Benjamin Lefranc 2 ,Jérôme Leprince 2 , and Michèle Baudy-Floc’h 11 UMR CNRS 6226, ICMV, University of Rennes 1, Rennes, France;2 INSERM U982, European Institute for Peptide Research,University of Rouen, Mont-Saint-Aignan, FranceIntroductionAza-β 3 -peptides, mixing α- and aza-β 3 -amino acids (the aza analogs of β 3 -amino acids),represent an exciting type of peptidomimetics [1,2]. In particular, they show a strongerresistance to degradation by proteases in vivo and a better bioavailability in comparisonwith peptides. We have also shown that an aza-β 3 -amino acid induces a N-N turn orhydrazino turn, stabilized by an eight-membered-ring intramolecular hydrogen bondbetween the carbonyl acceptor group of the residue i-1 and the amide proton of the residuei+1. Interestingly, this N-N turn promotes different conformations such as γ and β turn [3].On the other hand, 26RFa, a neuropeptide of the RFamide superfamily, exhibits highaffinity for GPR103 and induces a potent orexigenic effect in mice [4]. 26RFa (20-26)(GGFSFRF-NH 2 ), whose sequence is strictly conserved across species, is about 75 timesless potent than 26RFa to mobilize [Ca 2+ ] i in GPR103-transfected cells. In this study, azaβ3 moieties may become useful tools to increase interactions of 26RFa with his G-proteincoupled receptor GPR103. In continuity of aza-β 3 scan, we explore and develop procedures(a) to synthesize aza-β 3 homo serine (aza-β 3 -Hse) protected derivatives (Figure 1); (b) toinsert them in the 26RFa (20-26) sequence in position 23; and (c) to deprotect [aza-β 3 -Hse(R)] 23 RFa (20-26) by selective R-group cleavage. During the synthesis of the monomeraza-β 3 -Hse, some problems occured as well as during its side chain deprotection. We willpresent in this paper the synthesis of Fmoc-aza-β 3 -Hse(R)-OH, the incorporation of thissurrogate into the heptapeptide, and finally the side chain deprotection attempts, inparticular the microwave-assisted strategy.Results and DiscussionTo prepare Fmoc-aza-β 3 -Hse(R)-OH we need to conveniently protect the hydroxy group ofthe diacetal otherwise side reactions can occur. As we are using the Fmoc strategy for thepeptide synthesis, the hydroxy group was first protected as a methoxy ethyl ether usingchloromethyl ethyl ether and sodium hydride. The protected diethyl acetal was then treatedwith aq. HCl in tetrahydrofuran (THF), to give protected aldehyde in low yield (5%, Table1). So, different protections (Bn, All and Z) have been investigated to release protectedaldehydes and to reach the desired hydrazones by condensation with the Fmoc hydrazine(Table1). Reduction of the crude mixture with sodium cyanoborohydride gave the requiredN,N'-disubstituted hydrazine (R = CH 2 OEt, Bn, All, Z). Finally, reductive amination ofglyoxilic acid leads to the final monomer Fmoc-aza-β 3 -Hse(R)-OH (R=CH 2 OEt, Bn, All, Z).The aim of this work consists to use the Fmoc-aza-β 3 -Hse(R)-OH analog in SPPS withthe help of automatic microwave-assisted synthesizer. The Fmoc/t-butyl strategy on rinkamide resin and the TBTU activation were implemented to prepare the aza-β 3 -peptide26RFa (20-26) with aza-β 3 -Hse(R) insertion at position 23. Several methods were investigatedto deprotect the hydroxyl derivative residues. First, different classical strategies were testedon aza-β 3 -peptidyl resin without success.EtOOHEtONaH, 0°CRClOEtOROROHCl 2N25-30 °CFmocHNOEtH +FmocNH-NH 2NHORNaBH 3 CNHCl, 2NFmocHNNHROOHCCO 2 HNaBH 3 CNHCl, 2NRON CO 2 HFmocHNFmoc-aza β 3 Hse (OR)-OHFig. 1. Synthesis of Fmoc-azaβ 3 Hse(R)-OH.94
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Peptides 2010Tales of PeptidesProce
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Peptides 2010Tales of PeptidesProce
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IntroductionWe had the distinct hon
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Scientific programIn planning the 3
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31 st EUROPEAN PEPTIDE SYMPOSIUMSep
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published by John Wiley & Sons as a
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The Josef Rudinger AwardThis award
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Young Investigators' SymposiumThe y
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xxiv
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Design of Peptidyl-Inhibitors for G
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Synthetic Antifreeze Glycopeptide A
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Synthesis and Oxidative Folding of
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Convergent Syntheses of Huprp106-12
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Bactericidal Activity of Small Beta
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Bradykinin Analogues Acylated on Th
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Antimicrobial Activity of Small 3-(
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Interaction of Curcumin with A-Synu
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Fluorescent and Luminescent Fusion
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Cellular Expression of the Human An
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2D IR Spectroscopy of Oligopeptides
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large, non-redundant subset of prot
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The aberrantly glucosylated peptide
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Table 1. Proline cis/trans ratios o
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Table 1. Yields, UV-vis absorption
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Table 1. Purity of the targeted tri
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processes are blocked. Interestingl
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(tb4 n ,1 m )MTII(tb1 n ,4 m )MTIIF
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Fig. 2. a) Part of the 400 MHz HR-M
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Once printed, the amino acid partic
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A) PSA, few seconds73B) PSA, 45 min
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short β strands. In contrast, nume
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neg. control Cs9-Rhd MM-218Fig. 2.
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Table 1. The general structure of t
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% ID in the liver 1 h p.i.100908070
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Peptidyl phosphoranes were first re
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obtained from the same sardines and
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MccJ25 variants were produced by si
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Fig. 2. Proposed signaling mechanis
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Table 1. mCD4-HS12 antiviral activi
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Subject index(S)-2-(1-adamantyl)gly
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chip 18chiral triazine condensing r
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heat stress 348helical conformation
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O-acyl isopeptide method 112obesity
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SH2-ligands 210short collagen-relat
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Author indexAboye, Teshome Leta 142
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Chi, Hongfang 480Chiche, Laurent 6C
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Geronikaki, Athina 444Gessmann, Ren
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Kostova, Kalina 528Kotzia, Georgia
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Nagata, Koji 162Nagayev, Igor Yu. 5
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Salvarese, Nicola 518Sammet, Benedi
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Vauquelin, Georges 138Veiga, Ana Sa
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