|Title:||Reductive alkylation of glycopeptide antibiotics|
|Abstract:||This invention is concerned with improved processes for reductive alkylation of glycopeptide antibiotics. The improvement residing in providing a source of copper which results in the initial production of a copper complex of the glycopeptide antibiotic. Reductive alkylation of this complex favors regioselective alkylation and increased yields. Copper complexes of the glycopeptide antibiotic starting materials and of the alkylated products are also part of the invention.|
|Inventor(s):||Berglund; Richard Alan (Lafayette, IN), Lockwood; Nancy Anne (Mountlake Terrace, WA), Magadanz; Howard Eugene (Lafayette, IN), Zheng; Hua (Lafayette, IN)|
|Assignee:||Eli Lilly and Company (Indianpolis, ID)|
|Filing Date:||Nov 12, 1997|
|Claims:||1. A method for reductively alkylating a glycopeptide antibiotic comprising an amine-containing saccharide at N.sup.4 and one or more other amines, which comprises reacting a soluble copper complex of the glycopeptide antibiotic with a ketone or aldehyde in the presence of a reducing agent which is sodium cyanoborohydride or pyridine.cndot.borane complex. |
2. A method of claim 1 which is conducted in methanol.
3. A method of claim 2 in which the soluble copper complex of the glycopeptide antibiotic is prepared in situ from the glycopeptide antibiotic and a soluble form of copper.
4. A method of claim 3 wherein the glycopeptide antibiotic is a vancomycin type glycopeptide antibiotic.
5. A method of claim 4 wherein the glycopeptide antibiotic is A82846B.
6. A method of claim 5 wherein the aldehyde is 4'-chloro-4-biphenylcarboxaldehyde.