10.1016/j.bmcl.2009.04.135
The research focuses on the synthesis, cleavage, and antifungal activity of novel, water-soluble ester prodrugs of the antifungal triazole CS-758, aimed at developing an injectable antifungal agent for severe deep mycoses in hospitalized patients. The study describes the synthesis of several esters of CS-758, with a particular emphasis on phosphoryl ester 1a, which demonstrated good water solubility and efficient conversion to CS-758 in human liver microsomes and rats. The experiments involved various chemical reactions, including phosphorylation, oxidation, and esterification, utilizing reagents such as diallyl diisopropylphosphoramidite, t-butyl hydroperoxide, and bis(triphenylphosphine)dichloropalladium. The synthesized compounds were analyzed for their water solubility and ability to release CS-758 in vitro using human plasma and liver microsomes, and in vivo by administering the prodrugs to rats and measuring the bioavailability and conversion to CS-758. The antifungal activity of the prodrug 1a was evaluated in a murine systemic Candida albicans infection model, showing comparable or slightly superior effects to orally administered CS-758.
10.1055/s-0035-1560185
The study focuses on the reaction of N-arylpyrrolidine derivatives with 70% aqueous tert-butyl hydroperoxide (T-HYDRO) in the presence of sodium acetate trihydrate (NaOAc·3H2O) to produce tetracyclic amines via the cycloaddition of iminium ion and enamine intermediates formed in situ in cyclohexane solvent. The reaction yields tetracyclic amines in 59–78% yields, and the iminium ion intermediate can further react with potassium tert-butoxide (t-BuOK) in methanol to give cyclic amides in 85–88% yields or undergo alkylation to give nitromethyl products in 74–79% yields using t-BuOK and nitromethane in methanol. The purpose of these chemicals is to facilitate the formation of complex amine structures, which are important in organic synthesis and have potential applications in the synthesis of polycyclic amines and natural products.
10.1021/acs.joc.7b01516
The research focuses on the copper-catalyzed oxidative coupling of β-keto esters with N-methylamides to synthesize symmetrical 2,3,5,6-tetrasubstituted pyridines through a formal [2+2+1+1] cycloaddition. The process involves a domino sequence of cross-dehydrogenative coupling (CDC), C-N cleavage, Michael addition, condensation, and oxidative aromatization, constructing multiple C-C and C-N bonds in a single pot. The study utilized a variety of reactants, including different β-keto esters and N-methylamides, with ammonium acetate serving as the nitrogen source and tert-butyl hydroperoxide (TBHP) as the oxidant. The copper catalyst, specifically Cu2O, was optimized through various experiments to achieve the best yield of the desired pyridine products. Analyses such as NMR spectroscopy, GC-MS, HRMS, IR spectroscopy, and UV spectroscopy were employed to characterize the synthesized compounds and confirm the structure and purity of the products. Preliminary mechanistic studies, including kinetics isotope effect (KIE) and D-labeling experiments, suggested that the C(sp3)-H bond cleavage of N-methylamides was the rate-determining step and that the pyridine C-4 framework was derived from N-methylamides.
10.1007/s10600-007-0065-6
The research focuses on the synthesis of N-methyl urocanates of hydroxy derivatives of isocembrol, which are proposed biomimetics of taxol and exhibit cytotoxic activity similar to eleutherobin and sarcodictyins. The experiments involved stereospecific hydroxylation of isocembrol to prepare alcohols, which were then esterified into N-methylurocanates. Key reactants included isocembrol, t-butylhydroperoxide (TBHP), VO(acac)2, LiAlH4, (i-Bu)2AlH, SeO2, and N-methylurocanic acid, among others. The analyses used to characterize the products and intermediates were primarily nuclear magnetic resonance (NMR) spectroscopy, including both proton (PMR) and carbon (13C NMR) variants, as well as thin-layer chromatography (TLC), optical rotation measurements, and melting point determinations. These techniques were crucial in establishing the regio- and stereochemistry of the synthesized compounds.
10.1021/ol101618u
The research focuses on the development of a Pd-catalyzed method for direct C-H bond acylation through cross-coupling of aryl ketone O-methyl oximes with aldehydes, utilizing tert-butyl hydroperoxide (TBHP) as an oxidant. The study explores the ortho-selective C-H activation using oximes as a directing group, which results in the formation of diaryl ketones with excellent regioselectivity and functional group tolerance. The experiments involved the use of various aryl ketone O-methyl oximes and aldehydes, both aliphatic and heteroaromatic, to synthesize a diverse range of diaryl ketones. The reactions were optimized using different palladium catalysts, solvents, and reaction conditions to achieve good to excellent yields. The analyses used to determine the success of the reactions included gas chromatography with flame ionization detection (GC-FID) for yield determination, X-ray crystallography for establishing the molecular structure of the products, and NMR analysis to monitor the reaction progress and decomposition of starting materials. The study also proposed a plausible mechanism involving the generation of acyl radicals by reactive oxygen radicals and their subsequent reaction with palladacycles to form the product ketones.
O, 
C
