E. N. Olsuf’eva2, S. E. Solov’eva, M. I. Reznikova, A. M. Korolev, and M. N. Preobrazhenskaya
Gause Institute of New Antibiotics, Russian Academy of Medical Sciences,
ul. B. Pirogovskaya 11, Moscow, 119021 Russia
Received July 3, 2012; in final form, August 3, 2012
Abstract—The coupling reagent (benzotriazole-1-yl)oxy-tris(pyrrolidino)phosphonium hexafluorophosphate
(PyBOP) is widely used for the synthesis of different peptides and their amides, particularly carboxamides of
glycopeptide antibiotics of the vancomycin or teicoplanin groups. The amidation reaction of the carboxyl group
of the seventh amino acid residue (AA7) in antibiotics in the presence of PyBOP is not usually accompanied
by the formation of significant amounts of byproducts. However, the amidation of eremomycin (I) with bulky
amines (e.g., decyl amine and adamantyl amine) in the presence of PyBOP at pH ~8.5 (Et3N or (i-Pr)2EtN)
yielded N-unsubstituted carboxamide of eremomycin (Ia) as an admixture. The interaction of asparagine-
containing antibiotics (eremomycin or vancomycin) with the excess of PyBOP and Et3N (pH ~8.5) in the
absence of amine or ammonia led to the formation of still larger amounts of corresponding unsubstituted AA7-
amides (~20%). Their structure was determined by 1H NMR and ESI MS methods and confirmed by comparing
with authentic samples. It is assumed that the amide group of the asparagine residue (AA3) is the source of
ammonia in the unususal amidation reaction of Asn-containing antibiotics.
Keywords: glycopeptides, eremomycin, vancomycin, amidation reaction, PyBOP, asparagine
DOI: 10.1134/S106816201302009X
Pleiades Publishing home page | journal home page | top
If you have any problems with this server, contact webmaster.