Edwin Jao

Sch 51048, a novel broad-spectrum orally active antifungal agent: Synthesis and preliminary structure-activity profile

Abstract Synthesis of Sch 51048, a novel orally active azole antifungal, is described. Based on its superior oral efficacy over other available agents against a variety of fungal pathogens in normal and immunocompromised animal infection models, Sch 51048 is a subject for possible clinical evaluation.

Aqueous Diels-Alder reactions of electron deficient 2-arylfurans: a highly stereoselective route to 2,2,5-trisubstituted tetrahydrofurans towards a novel class of orally active azole antifungals

Aqueous Diels-Alder reactions 1 of halogenated 2-arylfurans with acetylenedicarboxylates made available previously inaccessible adducts (2, 2a, 7, and 8) which were successfully elaborated in a general stereocontrolled route to the title compounds

[3+2] Cycloaddition of trimethylenemethane (TMM) to α,β-unsaturated γ-lactam. Preparation of 5,5-fused proline surrogates

Abstract Unsaturated lactam derived from ( S )-pyroglutaminol undergoes a totally stereoselective cycloaddition reaction with (2-(acetoxymethyl)-3-allyl)trimethylsilane in the presence of Pd(P(O i Pr) 3 ) 4 in refluxing toluene. This step was efficiently used to introduced the 5,5-fused framework desired for the preparation of novel proline surrogates.

TOTAL SYNTHESIS OF THE ANTIFUNGAL CYCLIC DEPSIPEPTIDES SCH 57697 AND AUREOBASIDIN A

Abstract A novel cyclic depsinonapeptide antifungal 1a (Sch 57697) and its isomer 1b were synthesized by a fragment coupling approach and this methodology was applied to the total synthesis of the natural product aureobasidin A. Synthetic strategies for coupling of N-methyl amino acids with minimal racemization are discussed. Biological evaluation of isomers 1a and 1b demonstrated the importance of chirality at the β-hydroxy-N-methylvaline (OHMeVal) position.

Structure elucidation of Sch 49088, a novel everninomicin antibiotic containing an unusual hydroxylamino-ether sugar, everhydroxylaminose

Abstract Degradation of Sch 49088 ( 1 ) provided a novel, highly functionalized O-substituted hydroxylamine-containing sugar, everhydroxylaminose 11 isolated as a β-OMe glycoside. Notably the two acid sensitive orthoester moieties in the intact antibiotic 1 co-exist in the presence of three phenolic groups and a free carboxylic acid group.

Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034

Crystal structures of protease/inhibitor complexes guided optimization of the buried nonpolar surface area thereby maximizing hydrophobic binding. The resulting potent tripeptide inhibitor is in clinical trials.