Lipodepsipeptide antibiotics and methods of preparation
AssigneeBioSource Pharm, Inc.
InventorsRichard A. Leese, William V. Curran, Donald B. Borders
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Abstract
Novel cyclodepsipeptide intermediates have been prepared from the A21978 complex and used to synthesize new lipodepsipeptide antibiotics. The three intermediates can be readily derivatized to give new families of antibiotics that have potent antibacterial activity against gram positive bacteria.
Claims11
A method for preparing an intermediate for use in the synthesis of a lipodepsipeptide antibiotic, including the steps of:
- (a) Obtaining an A21978 complex having a cyclic depsipeptide unit by fermentation of Streptomyces roseosporus;
- (b) Protecting the orinithine amino group of the A21978 anti-biotic complex;
- (c) Treating the product from the reaction of step (b) with a deacylase enzyme to provide a single protected peptide;
- and
- (d) Using a modified Edman degradation method or enzymatic reactions to obtain a protected intermediate in the form of a cdpeptide, by reducing in size by one to three amino acids the exocyclic tripeptide side chain of the depsipeptide unit of said complex.
An antibacterial compound prepared from a chemically derivatized protected form of cdpeptide, having the following structure, where Y equals P or hydrogen:
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Protected cdpeptide compounds chosen from the group consisting of those designated cdpeptide, cdpeptide-1 and cdpeptide-2, as represented in the following embodiment, and which can be used to synthesize a lipodepsipeptide antibiotic:
- H-cdpeptide-P
- H-(X3)-cdpeptide-P
- H-(X2)(X3)-cdpeptide-P
- for all three cases H is hydrogen, X2 is asparaginyl, X3 is apartyl and P is a protective group.
Dependencies are inferred from the claim text.