Mark J. Zweifel

Glycopeptide antibiotic derivatives

The present invention provides glycopeptide antibiotic derivative compounds. These derivative compounds possess antibacterial activity aginst a wide variety of bacteria, including activity against vancomycin-resistant isolates. Methods of making and using these glycopeptide antibiotic derivative compounds are also provided.

Syntheses and antifungal activity of pseudomycin side-chain analogues. Part 1.

We have described herein the syntheses of three novel series of aromatic ring containing pseudomycin side-chain analogues. Preliminary biological evaluations of these analogues clearly indicate that it is possible to synthesize rigid pseudomycin side-chain analogues without compromising in vitro antifungal activity.

Syntheses and biological evaluation of novel pseudomycin side-chain analogues. Part 2.

A series of aliphatic side-chain analogues of pseudomycin was synthesized and evaluated during the course of our side-chain SAR effort. We found that several of the pseudomycin side-chain analogues (e.g., 10) exhibited good in vitro activity against all three major fungi responsible for systemic fungal infections.

Trimethylamine N-oxide: A novel reagent for the promotion of the retro-aldol reaction of R106-1 (LY295337)

Abstract The retro-aldol reaction of R106-1 (LY295337), 1 using trimethylamine N-oxide (TNO) facilitates the removal of the tertiary hydroxy group generating R106-sarcosine, 2 a key synthetic intermediate. The reagent is highly reproducible and provides high yields with no major side products. A side by side comparison of TNO vs. traditional bases is described.

Studies towards the synthesis of radiolabeled R106-1(LY295337)

A unique semisynthetic pathway has been used as a route to acquire radiolabeled material of a complex natural product, R106. The retro-aldol reaction of R106-1 gave a key intermediate R106-sarcosine that was used in a subsequent aldol reaction to incorporate acetone-[2- 14 C].