Princeton University

Robert Kerns

Daniel E Kahne

Seketsu Fukuzawa

Min Ge

Christopher Thompson

A glycopeptide of the formula A-A-A-A-A-A-A, in which each dash represents a covalent bond; wherein Acomprises a modified or unmodified &#x3b1;-amino acid residue, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl; wherein each of Ato Acomprises a modified or unmodified &#x3b1;-amino acid residue, whereby (i) Ais linked to an amino group on A, (ii) each of A, Aand Abears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) Abears a terminal carboxyl, ester, amide, or N-substituted amide group; A chemical library comprising a plurality of the glycopeptides of the invention. A method for preparing a glycopeptide by glycosylation of an aglycone derived from a glycopeptide antibiotic. A method for preparing a glycopeptide by preparing a pseudoaglycone from a glycopeptide antibiotic and glycosylating the pseudoaglycone.

Glycopeptide antibiotics, combinatorial libraries of glycopeptide antibiotics and methods of producing same

Methods for preparing a glycopeptide are disclosed. The methods comprise the steps of selecting a protected glycopeptide of the formula A-A-A-A-A-A-A, wherein the groups Ato Acomprise the heptapeptide structure of naturally occurring vancomycin; at least Ais linked to a glycosidic group which has a hexose residue linked to A; and the protected glycopeptide has no free amino or carboxyl groups and has a free primary hydroxyl group only at the 6-position of said hexose residue. The protected glycopeptide is contacted with a compound of the formula ArSOG where Ar is an aryl group and G is a leaving group under conditions effective to allow reaction of said free primary hydroxyl group to form a glycopeptide sulfonate ester; and the glycopeptide sulfonate ester is contacted with a nucleophile under conditions effective to allow displacement of a sulfonate group to produce a substituted glycopeptide.

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Troy, MI, United States of America

Robert Kerns