A synthesis of (1E,3E)-TMS dienes from keto-xanthates via Chugaev-type elimination.

An efficient route leading to exclusively (1E,3E)-TMS dienes is described. Radical xanthate addition of keto-xanthates to vinyltrimethylsilane followed by one-pot Chugaev elimination/cyclization and in situ oxidation with m-CPBA afforded the corresponding TMS 2-sulfolenes. Isomerization to 3-sulfolenes by the action of DBU with the extrusion of sulfur dioxide in refluxing toluene gave the titled (1E,3E)-TMS dienes.

Quantification of Fosfomycin in Combination with Nine Antibiotics in Human Plasma and Cation-Adjusted Mueller-Hinton II Broth via LCMS.

Fosfomycin-based combination therapy has emerged as an attractive option in our armamentarium due to its synergistic activity against carbapenem-resistant Gram-negative bacteria (CRGNB). The ability to simultaneously measure fosfomycin and other antibiotic drug levels will support in vitro and clinical investigations to develop rational antibiotic combination dosing regimens against CRGNB infections. We developed an analytical assay to measure fosfomycin with nine important antibiotics in human plasma and cation-adjusted Mueller-Hinton II broth (CAMHB). We employed a liquid-chromatography tandem mass spectrometry method and validated the method based on accuracy, precision, matrix effect, limit-of-detection, limit-of-quantification, specificity, carryover, and short-term and long-term stability on U.S. Food & Drug Administration (FDA) guidelines. Assay feasibility was assessed in a pilot clinical study in four patients on antibiotic combination therapy. Simultaneous quantification of fosfomycin, levofloxacin, meropenem, doripenem, aztreonam, piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam, cefepime, and tigecycline in plasma and CAMHB were achieved within 4.5 min. Precision, accuracy, specificity, and carryover were within FDA guidelines. Fosfomycin combined with any of the nine antibiotics were stable in plasma and CAMHB up to 4 weeks at -80 °C. The assay identified and quantified the respective antibiotics administered in the four subjects. Our assay can be a valuable tool for in vitro and clinical applications.

Synthesis of water-tolerant indium homoenolate in aqueous media and its application in the synthesis of 1,4-dicarbonyl compounds via palladium-catalyzed coupling with acid chloride.

The first water-tolerant, ketone-type indium homoenolate was synthesized via the oxidative addition of In/InCl(3) to enones. The reaction proceeds exclusively in aqueous media. Both indium and indium(III) chloride are necessary for the smooth conversion of the reaction. Similar results were obtained when InCl or InCl(2) was used in place of In/InCl(3). The synthetic utility of the indium homoenolate was demonstrated through the synthesis of 1,4-dicarbonyl compounds via palladium-catalyzed coupling of indium homoenolate with acid chloride.

Free-radical variant for the synthesis of functionalized 1,5-diketones.

A free-radical approach for the synthesis of functionalized 1,5-diketones has been accomplished through an effective combination play between alkenylacylphosphonates and keto-xanthates as radical surrogates of enolates and enones, respectively.

Direct synthesis of ester-containing indium homoenolate and its application in palladium-catalyzed cross-coupling with aryl halide.

An efficient method for the synthesis of ester-containing indium homoenolate via a direct insertion of indium into ß-halo ester in the presence of CuI/LiCl was described. The synthetic utility of the indium homoenolate was demonstrated by palladium-catalyzed cross-coupling with aryl halides in DMA with wide functional group compatibility.

Palladium-catalyzed cross-coupling of indium homoenolate with aryl halide with wide functional group compatibility.

An efficient palladium-catalyzed cross-coupling of indium homoenolate with aryl halide is described. The reactions proceeded efficiently in DMA at 100 °C to afford the desired products of ß-aryl ketones in moderate to good yields. Various important functional groups including COR, COOR, CHO, CN, OH, and NO(2) can be well tolerated in the protocol.