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Table 1. Diastereoselectivity studies of the Pictet-Spengler reactionAminoaldehydeArylethylamineCbz-L-Ala-Hcis/transratio [%]Cbz-L-Ile-Hcis/ transratio [%]Cbz-D-Ala-Hcis/transratio [%]Cbz-D-Leu-Hcis/transratio [%]α-Trp-OCH 3 35/65 0/100 100/0 100/0α-Trp-Ala-OCH 3 26/74 0/100 100/0 100/0α-Trp-Leu-OCH 3 28/72 0/100 100/0 100/0β 3- h-Trp-OCH 3 60/40 0/100 100/0 100/0β 3- h-Trp-Ala-OCH 3 46/54 0/100 100/0 100/0β 3- h-Trp-Leu-OCH 3 32/68 0/100 100/0 100/0Pictet-Spengler condensation of L- and D-α-aminoaldehydes as carbonyl components withmethyl ester and N-terminal α-Trp or β 3 -homo-Trp dipeptides as arylethylamine substratesled to 1,3-disubstituted 1,2,3,4-tetrahydro-β-carbolines. During the Pictet-Spengler reactiona new stereogenic center was created and the mixture of cis/trans products was obtained. Itwas confirmed by 1H and 2D NMR (COSY, ROESY) spectra. The results of reactions aresummarized in Table 1. The ratio of cis/trans diastereomers depended on the stereogeniccentre of used aminoaldehyde. For β 3 -homo-Trp-OCH 3 reaction with Cbz-L-Ala-H led tothe opposite stereoselectivity in comparison to α-Trp-OCH 3 and cis isomer was the mainproduct. The stereoselectivity in the reaction of β 3 h-Trp-OCH 3 with Cbz-L-Ile-H andD-aminoaldehydes was the same as for α-Trp-OCH 3 . In the reaction with Cbz-L-Ile-H onlytrans isomer was obtained. The reactions with D-aminoaldehydes were totally selective andonly cis diastereomer was formed.The conformation of newly created 6-membered ring in 1,3-disubstituted 1,2,3,4-tetrahydro-β-carbolines was determined by 2D NMR ROESY spectra. It depended on thesize of substituents. In the case of trans isomers small substituents (ester moiety) wereaxially located, big ones (peptide moieties) were equatorially located. Cis isomers adoptedthe conformation with both substituents equatorially located [5].During the Pictet-Spengler reaction with the use of L-β 2 -homo-Trp-OCH 3 a new7-membered ring was created (Figure 2). Two different diastereoisomers were produced asa result of reaction with L-aminoaldehyde and D-aminoaldehyde. Chemical shifts of -OCH 3signal in 1H NMR spectra confirmed that obtained compounds were differentdiastereoisomers. The stereoselectivity of these reactions is under investigation.Fig. 2. Pictet-Spengler reaction of β 2 -hTrp-OCH 3 .References1. Pictet, A., Spengler, T. Ber. Dtsch. Chem. Ges. 44, 2030-2036 (1911).2. Pulka,, K., Kulis P., Tymecka, D., Frankiewicz, L., Wilczek, M., Kozminski, W., Misicka, A.,Tetrahedron 64, 1506-1514 (2008).3. Koch, K., Podlech, J. Synthetic Communications 35, 2789-2794 (2005).4. Moumne, R., Larregola, M., Boutadla,, Y., Lavielle, S., Karoyan, P. Tetrahedron Letters 49, 4704-4707 (2008).5. Pulka, K., Slupska, M., Misiak, M., Lipkowska, Z., Kozminski, W., Misicka, A., 1,3-Disubstituted1,2,3,4-tetrahydro-β-carbolines as peptidomimetics of tryptophan: synthesis and conformationalanalysis (Poster in the 30 th European Peptide Symposium), Helsinki, Finland, 2008.243