Preparation and antifungal activity of fusacandin analogs: C-6′ sidechain esters

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 7, 1996, Pages 819-822

  Yeung, Clinton M ^a   Klein, Larry L ^a   Lartey, Paul A ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIFUNGAL AGENT; FUSACANDIN A; FUSACANDIN B; FUSACANDIN DERIVATIVE; PAPULACANDIN B; UNCLASSIFIED DRUG;

ANTIFUNGAL ACTIVITY; ARTICLE; CANDIDA ALBICANS; CHIRALITY; CONTROLLED STUDY; DRUG SYNTHESIS; MINIMUM INHIBITORY CONCENTRATION; SERUM; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

EID: 0029996271     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00113-8     Document Type: Article

References (20)

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3. The Merck group later reported another similar series: VanMiddlesworth, F.; Omstead, M. N.; Schmatz, D.; Bartizal, K.; Fromtling, R.; Bills, G.; Nollstadt, K.; Honeycutt, S.; Zweernik, M.; Garrity, G.; Wilson, K. E. J. Antibiotics 1991, 44, 45; VanMiddlesworth, F.; Dufresne, C.; Smith, J.; Wilson, K. E. Tetrahedron 1991, 47, 7563.
4. The Merck group later reported another similar series: VanMiddlesworth, F.; Omstead, M. N.; Schmatz, D.; Bartizal, K.; Fromtling, R.; Bills, G.; Nollstadt, K.; Honeycutt, S.; Zweernik, M.; Garrity, G.; Wilson, K. E. J. Antibiotics 1991, 44, 45; VanMiddlesworth, F.; Dufresne, C.; Smith, J.; Wilson, K. E. Tetrahedron 1991, 47, 7563.
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13. The (S) absolute stereochemistry at C-7‴ was established via degradation studies: methanolysis of 2, followed by (R)-naphthylethylisocyanate, ozonolysis, and reduction to diol carbamate. This diol was compared to both (R)- and (S)-butanetriol carbamates prepared from commercially available materials. We appreciate HPLC help from G. Brill and Dr. R. Chen.
14. Dr. K. Marsh and Dr. H. W. Hua, unpublished results.
15. Klein, L. L.; Yeung, C. M. Unpublished results.
16. No removal of the C-3 sidechain occurs under these conditions probably due to the hindrance from proximal glycoside and TES groups. Under forcing conditions only 1,4-addition to this chain was observed.
17. Oh-e, T.; Miyaura, N.; Suzuki, A. J. Org. Chem. 1993, 58, 2201.
18. 1H NMR, high resolution mass spectra, and HPLC purity >90%.
19. Shadomy, S.; Pfaller, M. In Manual of Clinical Microbiology 5th ed.; Balows, A.; Hausler, W. J.; Herrmenn, K. L.; Isenberg, H. D.; Shadomy, H. J. Ed.; American Society for Microbiology; Washington, D.C. 1991; pp 1173-1183.
20. During the deprotection of 6m with TBAF, the C-4′ ethylbiphenyl analog was produced presumably due to an acyl migration. This analog showed poor activity thereby establishing the importance of the positioning of this sidechain.