Synthesis of vancomycin from the aglycon

Journal of the American Chemical Society

Volumn 121, Issue 6, 1999, Pages 1237-1244

  Thompson, Christopher ^a   Ge, Min ^a   Kahne, Daniel ^a  

^a PRINCETON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBOHYDRATE; VANCOMYCIN;

ANTIMICROBIAL ACTIVITY; ARTICLE; DRUG SYNTHESIS; GLYCOSYLATION;

EID: 0033577010     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja983504u     Document Type: Article

References (45)

1. The carbohydrates on vancomycin have been implicated in biological activity. See, for example: (a) Rodriguez, M. J.; Snyder, N. J.; Zweifel, M. J.; Wilkie, S. C.; Stack, D. R.; Cooper, R. D.; Nicas, T. I.; Mullen, D. L.; Butler, T. F.; Thompson, R. C. J. Antibiot. 1998, 51, 560. (b) Malabarba, A.; Nicas, T. I.; Thompson, R. C. Med. Res. Rev. 1997, 17, 69. (c) Williams, D. H. Nat. Prod. Rep. 1996, 469.
2. The carbohydrates on vancomycin have been implicated in biological activity. See, for example: (a) Rodriguez, M. J.; Snyder, N. J.; Zweifel, M. J.; Wilkie, S. C.; Stack, D. R.; Cooper, R. D.; Nicas, T. I.; Mullen, D. L.; Butler, T. F.; Thompson, R. C. J. Antibiot. 1998, 51, 560. (b) Malabarba, A.; Nicas, T. I.; Thompson, R. C. Med. Res. Rev. 1997, 17, 69. (c) Williams, D. H. Nat. Prod. Rep. 1996, 469.
3. The carbohydrates on vancomycin have been implicated in biological activity. See, for example: (a) Rodriguez, M. J.; Snyder, N. J.; Zweifel, M. J.; Wilkie, S. C.; Stack, D. R.; Cooper, R. D.; Nicas, T. I.; Mullen, D. L.; Butler, T. F.; Thompson, R. C. J. Antibiot. 1998, 51, 560. (b) Malabarba, A.; Nicas, T. I.; Thompson, R. C. Med. Res. Rev. 1997, 17, 69. (c) Williams, D. H. Nat. Prod. Rep. 1996, 469.
4. (a) Walsh, C. T.; Fisher, S. L.; Park, I.-S.; Prahalad, M.; Wu, Z. Chem. Biol. 1996, 3, 21.
5. For various hypotheses on how carbohydrate derivatives of vancomycin can overcome bacterial resistance, see, for example: (b) Sharman, G. J.; Try, A. C.; Dancer, R. J.; Cho, Y. R.; Staroske, T.; Bardsley, B.; Maguire, A. J.; Cooper, M. A.; O'Brien, D. P.; Williams, D. H. J. Am. Chem. Soc. 1997, 119, 12041.
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7. The vancomycin disaccharide has been synthesized by three different groups but has never been attached to the aglycon: (a) Dushin, R. G.; Danishefsky, S. J. J. Am. Chem. Soc. 1992, 114, 3471. (b) Nicolaou, K. C.; Mitchell, H. J.; van Delft, F. L.; Rubsam, F.; Rodriguez, R. M. Angew. Chem. 1998, 110, 1972. (c) Ge, M.; Thompson, C.; Kahne, D. J. Am. Chem. Soc. 1998, 120, 11014.
8. The vancomycin disaccharide has been synthesized by three different groups but has never been attached to the aglycon: (a) Dushin, R. G.; Danishefsky, S. J. J. Am. Chem. Soc. 1992, 114, 3471. (b) Nicolaou, K. C.; Mitchell, H. J.; van Delft, F. L.; Rubsam, F.; Rodriguez, R. M. Angew. Chem. 1998, 110, 1972. (c) Ge, M.; Thompson, C.; Kahne, D. J. Am. Chem. Soc. 1998, 120, 11014.
9. The vancomycin disaccharide has been synthesized by three different groups but has never been attached to the aglycon: (a) Dushin, R. G.; Danishefsky, S. J. J. Am. Chem. Soc. 1992, 114, 3471. (b) Nicolaou, K. C.; Mitchell, H. J.; van Delft, F. L.; Rubsam, F.; Rodriguez, R. M. Angew. Chem. 1998, 110, 1972. (c) Ge, M.; Thompson, C.; Kahne, D. J. Am. Chem. Soc. 1998, 120, 11014.
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39. Ten equivalents of thiophenol was used to scavenge the cleaved sugars, which prevents byproduct formation and the loss of protecting groups from the aglycon.
40. 15 could not be completely purified, but the mass (ESI) was consistent with the structure shown.
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45. The allyl alcohol was included in the reaction in order to preveni the reduction of the allyl protecting groups on vancomycin by diimide, which may be present in hydrazine.