Jonathan W. Paschal

A83543A-D, unique fermentation-derived tetracyclic macrolides

Abstract A multi-factored complex of structurally-unique macrolides was isolated from culture broths of a new species of Saccharopolyspora. The core structure consists of a 5,6,5-cis-anti-trans-tricyclic ring system fused to a 12-membered macrocyclic lactone, which is further substituted by an amino- and a neutral sugar.

Synthetic studies on the furan ring of wortmannin

Abstract Synthetic studies on the fungal metabolite, wortmannin, were undertaken in an effort to gain insight into the structure activity relationships of wortmannin analogs on phosphatidylinositol-3′-kinase (PI-3-kinase). Our work has focused on the chemistry of the previously unexplored furan ring and has uncovered several interesting and novel chemical transformations, which are described herein.

Stereoselective synthesis of cis-substituted azetidinones from penicillin : a formal total synthesis of loracarbef

Abstract A new method for the synthesis of chiral azetidinones bearing a carbon-carbon bond at the 4-position is described. The preparation involves a stereoselective alkylation-reduction of a silylated 4-phenylsulfonyl azetidinone. The utility of this method was demonstrated by a formal total synthesis of loracarbef.

Serendipitous synthesis of novel dehydro- and dechloro-pseudomycin B (PSB) derivatives

The syntheses and preliminary investigation of antifungal activities of two dehydro PSB derivatives 8 and 10 as well as one 3-imido-9-dechloro PSB analogue 13 are described.

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.

Synthesis of a 3-keto bicyclic pyrazolidinone using a Curtius rearrangement

The synthesis of bicyclic pyrazolidinone 2 is described. Traditional methods for penem and cephem ring cyclization were found to be unsuccessful and new methodology using a Curtius rearrangement was utilized. The 3-enamine 11 was hydrolysed to the desired β-keto ester 2b without substantial loss of the t-BOC protecting group.