Vancosamines are

aminosugars In organic chemistry, an amino sugar is a sugar molecule in which a hydroxyl group has been replaced with an amine group. More than 60 amino sugars are known, with one of the most abundant being N-Acetylglucosamine, ''N''-acetyl--glucosamine (a 2- ...

that are a part of

vancomycin Vancomycin is a glycopeptide antibiotic medication used to treat certain bacterial infections. It is administered intravenously ( injection into a vein) to treat complicated skin infections, bloodstream infections, endocarditis, bone an ...

and other molecules within the vancomycin family of antibiotics. Vancosamine synthesis is encoded by the vancomycin (''vps'') biosynthetic cluster. Epivancosamine, a closely related aminosugar, is encoded by the

chloroeremomycin Chloroeremomycin is a member of the glycopeptide family of antibiotics, such as vancomycin. The molecule is a non-ribosomal polypeptide that has been glycosylated. It is composed of seven amino acids and three saccharide units. Although chloroe ...

(''cep'') biosynthetic cluster.

History

Vancosamine was first isolated by Lomakina ''et al'' in 1968. In 1972, Johnson ''et al'' were the first to identify and completely characterize vancosamine. Epivancosamine was subsequently isolated in 1988 by Hunt ''et al'' at

Eli Lilly Eli Lilly (July 8, 1838 – June 6, 1898) was a Union Army officer, pharmacist, chemist, and businessman who founded Eli Lilly and Company. Lilly enlisted in the Union Army during the American Civil War and recruited a company of men to ...

Biosynthesis

The biosynthesis of vancosamine and epivancosamine are identical, except in the last step. The enzymes that catalyze the reactions have been designated EvaA-E. A molecule of TDP-D-glucose enters the pathway via conversion to molecule 1 by an oxidoreductase enzyme and then a dehydratase enzyme. In the next step, EvaA dehydrates molecule 1 by deprotonating at 3-C to form and enolate, which then eliminates 2-OH, to form molecule 2. Molecule 2 is transformed into molecule 3 by tautomerizing to its keto form and then being transaminated by EvaB using L-Glu as the ammonia source and PLP as a cofactor. : Vancosamine_biosynth_part_1

EvaC then methylates molecule 3 at the 3-C to form molecule 4 by deprotonating to form an enolate intermediate, which then attacks a SAM methyl group in the active site of EvaC. EvaD then epimerizes molecule 4 at 5-C to form molecule 5. Finally, EvaE can form either epi/vancosamine by reduction using either

NADH Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an ade ...

NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require N ...

to reduce the carbonyl at 4-C. The stereochemical outcome is dependent on the EvaE that is encoded in the biosynthetic cluster. Vancomycin ''vps'' EvaE results in vancosamine, whereas

''cep'' EvaE results in epivancosamine. : Vancosamine_biosynthesis_part_2

The vancosamines are then used by the cell to synthesized vancomycin and related molecules. A glycosyltransferase attaches the amino sugar through α-1 ether linkages. Additional modifications are possible at the 3-C amino group to create ''N''-alkyl or ''N''-acyl derivatives of this sugar.

Total syntheses

Several syntheses of vancosamine have been published.Parker, K. A., Chang, W. "A Synthesis of L-Vancosamine Derivatives from Non-Carbohydrate Precursors by a Short Sequence Based on the Marshall, McDonald, and Du Bois Reactions." ''Org. Lett.'' 2003, ''5'' (21), 3891-3893.

References

{{reflist Amino sugars

History

Biosynthesis

Total syntheses

See also

References