Vancosamine

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Vancosamine
File:Vancosamine and epivancosamine.png
Cyclohexane and chair depictions of vancosamine (top) and epivancosamine (bottom). Note the differing stereocenter at carbon 4.
Names
IUPAC name
(3S,4S,5S)-3-Amino-4,5-dihydroxy-3-methylhexanal
Other names
3-Amino-2,3,6-trideoxy-3-methyl-L-lyxo-hexopyranose
Identifiers
3D model (JSmol)
ChemSpider
  • InChI=1S/C7H15NO3/c1-5(10)6(11)7(2,8)3-4-9/h4-6,10-11H,3,8H2,1-2H3/t5-,6+,7-/m0/s1
    Key: IJSNCWAAHIVVGJ-XVMARJQXSA-N
  • CC(C(C(C)(CC=O)N)O)O
Properties
C7H15NO3
Molar mass 161.201 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Vancosamines are aminosugars that are a part of vancomycin 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 (cep) biosynthetic cluster.[1]

History

Vancosamine was first isolated by Lomakina et al in 1968.[2] In 1972, Johnson et al were the first to identify and completely characterize vancosamine.[3] Epivancosamine was subsequently isolated in 1988 by Hunt et al at Eli Lilly[4]

Biosynthesis

The biosynthesis of vancosamine and epivancosamine are identical, except in the last step.[5] 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.

File:Vancosamine biosynth part 1.png
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 or NADPH 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 chloroeremomycin cep EvaE results in epivancosamine.

File:Vancosamine biosynthesis part 2.png
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.[6][7][8]

See also

References

  1. ↑ Yim, G., Thaker, M. N., Koteva, K., Wright, G. "Glycopeptide antibiotic biosynthesis." The Journal of Antibiotics, 2017, 67, 31-41.
  2. ↑ Lomakina, N. N., Spiridonova, I. A., Bognár, R., Puksás, M., Sztaricskai, F. Antibiotiki. 1968, 13, 975.
  3. ↑ Johnson, A. W., Smith, R. M., Guthrie, R. D."Vancosamine: the Structure and Configuration of a Novel Amino-sugar from Vancomycin." J. C. S. Perkin I, 1972, 2153-2159.
  4. ↑ Hunt, A. H., Molloy, R. M., Debono, M., Occolowitz, J. L. "Isolation and Characterization of 4-epi-vancosamine." Tetrahedron Lett, 1988, 29, 1223-1226.
  5. ↑ Chen, H., Thomas, M. G., Hubbard, B. K., Losey, H. C., Walsh, C. T., Burkart, M. D. "Deoxysugars in glycopeptide antibiotics: Enzymatic synthesis of TDP-L-epivancosamine in chloroeremomycin biosynthesis." PNAS, 2000, 97 (22), 11942-11947
  6. ↑ Hauser, F. M., Ellenberger, S. R., Glusker, J. P., Smart, F. J., Carrell, H. L. "Stereoselective Syntheses or +/- Daunosamine, +/- Vancosamine, and +/- Ristosamine from Acyclic Precursors." J. Org. Chem. 1986, 51, 50-57.
  7. ↑ Nicolaou, K. C., Mitchell, H. J., van Delft, F. L., Rübsam, F., Rodrígruez, R. M. "Expeditious Routes to Evernitrose and Vancosamine Derivatives and Synthesis or a Model Vancomycin Aryl Glycoside." Angew. Chem. Int. Ed. 1998, 37, No 13/14, 1871-1874.
  8. ↑ 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.
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