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α-Selective Glycosylation Affords Mucin-Related GalNAc Amino Acids and Diketopiperazines Active on Trypanosoma Cruzi

Maristela B Martins-Teixeira, Vanessa L Campo, Monica Biondo, Renata Sesti-Costa, Zumira A Carneiro, João S Silva, Ivone Carvalho

Bioorg Med Chem. 2013 Apr 1;21(7):1978-87.

PMID: 23415086

Abstract:

This work addresses the synthesis and biological evaluation of glycosyl diketopiperazines (DKPs) cyclo[Asp-(αGalNAc)Ser] 3 and cyclo[Asp-(αGalNAc)Thr] 4 for the development of novel anti-trypanosomal agents and Trypanosoma cruzi trans-sialidase (TcTS) inhibitors. The target compounds were synthetized by coupling reactions between glycosyl amino acids αGalNAc-Ser 7 or αGalNAc-Thr 8 and the amino acid (O-tBu)-Asp 17, followed by one-pot deprotection-cyclisation reaction in the presence of 20% piperidine in DMF. The protected glycosyl amino acid intermediates 7 and 8 were, in turn, obtained by α-selective, HgBr2-catalysed glycosylation reactions of Fmoc-Ser/Thr benzyl esters 12/14 with αGalN3Cl 11, being, subsequently, fully deprotected for comparative biological assays. The DKPs 3 and 4 showed relevant anti-trypanosomal effects (IC50 282-124 μM), whereas glycosyl amino acids 1 and 2 showed better TcTS inhibition (57-79%) than the corresponding DKPs (13-25%).

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42410620 Fmoc-Ser(tBu)-OH-15N Fmoc-Ser(tBu)-OH-15N Price
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