Paul A. Lartey

On the communication of chirality from furanose and pyranose rings to monosaccharide side chains: anomalous results in the glucose series

Abstract The reactions of allyltrimethylsilane with dialdose derivatives occur, under catalysis by boron trifluoride etherale or titanium tetrachloride, with high stercosclectivity, thereby providing simple routes to the corresponding allyl carbinols. The sense of this Sakurai reaction is very dependent on the nature of the Lewis acid. The same aldehydes react with β-trimethylsilylethylidenetriphenylphosphorane to afford 3-trimethylsilylprop-1-ene-1-yl-furanosides and pyranosides. Reactions of these compounds with osmium tetroxide, followed by elimination of trimcthylsilanol, afford the corresponding vinyl carbinols.

Preparation and antifungal activity of fusacandin analogs: C-6′ sidechain esters

Abstract The preparation of C-6′ ester analogs of fusacandin ( 2 ) is described leading to derivatives exhibiting improved in vitro activity in the presence of mouse serum.

Discovery, SAR, synthesis, pharmacokinetic and biochemical characterization of A-192411: A novel fungicidal lipopeptide-(I)

The echinocandin class of cyclic lipopeptides has been simplified to discover potent antifungal compounds. Namely A-192411 shows good in vitro activity against common pathogenic yeasts and has an acceptable safety window in vivo. Discovery, limited SAR, synthesis, biochemical and pharmaco-dynamic profiles of A-192411 are presented.

Preparation and antibacterial activity of pyridopyridone analogs: C-1 modifications

Abstract Variation of the C-1 position of the pyridopyridone antibacterials shows a sensitivity to both size and electronic character of the substituent.

3H-labeling of prokinetic motilide ABT-229 for biodistribution and metabolism studies

The prokinetic drug candidate, ABT-229, has been successfully [ 3 H]-labeled in the macrolactone ring. This was accomplished with [ 3 H]-NaBH4 reduction of the 11-ketone analog in a four step synthetic sequence beginning with the drug candidate. The 3 H-labeled drug was obtained with specific activity of 9.0 Ci/mmol and radiochemical purity >99%. This constitutes the first methodology for 3 H-labeling of the macrolactone in an erythromycin derivative.

In vivo characterization of A-192411: a novel fungicidal lipopeptide (II)

The ability of the novel antifungal cyclic hexalipopetide A-192411 to treat fungal infections in rodents is presented. Efficacy was demonstrated against Candida albicans as both prolonged survival of systemically infected mice and clearance of viable yeasts from kidneys. The efficacy of A-192411, administered intraperitoneally, was equivalent to amphotercin B at a 4-fold lower dose by weight in the systemic candidiasis models in mice, while the efficacy of A-192441 administered intravenously was equivalent to amphotercin B by weight in the Candida pyelonephritis model in rats. A-192411 also slightly prolonged the survival of immunocompromised mice infected systemically with Aspergillus fumigatus.