Selective cleavage of vancosamine, glucose, and N-methyl-leucine from vancomycin and related antibiotics

Abstract

Reaction of vancomycin and related antibiotics with trifluoroacetic acid at -15°C for 40 h selectively cleaved the amino sugar vancosamine; the second sugar, glucose, was removed b y reaction with trifluoroacetic acid at 50°C for 3 h, and the N-terminal leucine moiety was cleaved using the Edman degradation procedure.

Enzymatic synthesis of vancomycin derivatives using galactosyltransferase and sialyltransferase

“…Enzymatic synthesis and analysis of novel glycosylated compounds from pseudo-vancomycin and vancomycin Compound 2, which was prepared by trifluoroacetic acid-treated cleavage of the monosaccharide, 3 was enzymatically galactosylated with the overexpressed b1,4-GalT using UDP-Gal as the glycosyl donor ( Figure 3a) to generate compound 6. Then the sialylation of 6 was carried out using overexpressed a2,3-SiaT and CMP-NueAc for compound 7.…”

“…1,2 The desvancosamine derivative of vancomycin, pseudo-vancomycin (2), which is 2-4 times less active than the parent antibiotic, was obtained as the major product by treatment with trifluoroacetic acid. 3 Recent enzymatic and chemoenzymatic alterations have revealed that vancomycin's disaccharide attachment may be one alteration route for new bioactive compounds. 4,5 Walsh group and coworkers showed regio-specific enzymatic reconstitution of the antibiotic chloroeremomycin from the heptapeptide aglycone by three glycosyltransferases, GtfA, GtfB and GtfC, 6 and a systematic utility of chemoenzymatic approaches to diversify complex natural product architectures by using glycopeptides glycosyltransferases, GtfD and GtfE, which are the most versatile enzyme for the synthesis of vancomycin analogs.…”

Chemistry, Biology, and Medicine of the Glycopeptide Antibiotics

“…Under acidic conditions, for example, vancomycin (1) yielded vancomycin aglycon (19) and its two carbohydrate components, vancosamine (20) and glucose (21) (Scheme 1). [97] Subjecting the aglycon to more drastic conditions yielded actinoidinic acid (22) and vancomycin acid (23). [98] Degradation studies of vancomycin also produced a nonbiologically active crystalline product CDP-I (24, Scheme 2).…”

Antibacterial activities and modes of action of vancomycin and related glycopeptides

“…In many cases, the first sugar is glucose, and the second sugar is an amino sugar, either L-vancosamine or L-4-epivancosamine. These two sugars can be cleaved selec- tively in a sequential manner (26). The desvancosamine derivatives of vancomycin, A51568A and M43A, and the corresponding aglycones have been obtained (26).…”

“…The state of methylation of the N-terminal leucine does not greatly affect the antibacterial activity of vancomycin. However, the removal of this crucial amino acid (5,26), needed for binding of the N-acyl-D-alanyl-D-alanine (acyl-D-ala-D-ala) carboxy terminus of UDP-N-acetylmuramylpentapeptide to the N-terminal leucine of vancomycin, completely destroys the antibacterial activity of vancomycin (see also Modes of Action section).…”