In Vitro and in Vivo Study of a Photostable Quinone Compound with Enhanced Therapeutic Efficacy against Chagas Disease.

Chagas disease, a neglected tropical disease caused by the protozoan Trypanosoma cruzi poses a significant health challenge in rural areas of Latin America. The current pharmacological options exhibit notable side effects, demand prolonged administration, and display limited efficacy. Consequently, there is an urgent need to develop drugs that are safe and clinically effective. Previously, we identified a quinone compound (designated as compound 2) with potent antiprotozoal activity, based on the chemical structure of komaroviquinone, a natural product renowned for its antitrypanosomal effects. However, compound 2 was demonstrated considerably unstable to light. In this study, we elucidated the structure of the light-induced degradation products of compound 2 and probed the correlation between the quinone ring's substituents and its susceptibility to light. Our findings led to the discovery of quinones with significantly enhanced light stability, some of which exhibiting antitrypanosomal activity. The most promising compound was evaluated for drug efficacy in a mouse model of Chagas disease, revealing where a notable reduction in blood parasitemia.

Hexylsilane-mediated direct amidation of amino acids with a catalytic amount of 1,2,4-triazole.

In this study, we report amino acid amidation using hexylsilane and a catalytic amount of 1,2,4-triazole. The conventional protection/deprotection method for the α-amino group of amino acids is not required. The corresponding α-amino amides were obtained in moderate to good yields with low to no racemization.

Exploratory study of oxatomide derivatives with high P2X7 receptor inhibitory activity.

Various oxatomide derivatives were designed and synthesized to develop novel P2X7 receptor (P2X7R) antagonists. Evaluation for in-vitro P2X7R antagonist assay showed that DPM-piperazine moiety of oxatomide was required to maintain an inhibitory activity. The structure of both alkyl chains and aromatic head groups strongly affected P2X7R inhibitory activity, and the analogue, with C4-type saturated alkyl chain and a non-substituted or fluorine-substituted indole, was 7.3 to 6.4 times more potent as a P2X7R antagonist than oxatomide.

Synthesis and Evaluation of Quinone Derivatives for Activity against Trypanosome cruzi.

A series of quinone derivatives with a variety of side chains were synthesized. These synthetic quinone compounds were evaluated for in vitro antitrypanosomal activity against trypomastigotes and amastigotes of Trypanosoma cruzi, the causative agent of Chagas disease. Measurement of solubility of quinones and their ability to permeate cell membranes were assessed to address their possible use as oral drugs. Some synthesized compounds exhibited potent antitrypanosomal activity. However, most compounds with a promising activity showed poor solubility that did not seem suitable for oral usage. Meanwhile, compound 5a, an N-tert-butoxycarbonylpiperidine derivative, exhibited good antitrypanosomal activity, ability to permeate membranes, and good solubility.

Catalyst-controlled site-selective asymmetric epoxidation of nerylamine and geranylamine derivatives.

Novel catalysts for site- and enantioselective epoxidation of nerylamine and geranylamine derivatives have been developed. Although mCPBA oxidation took place selectively at the more electron-rich double bond to give the 6,7-epoxides, these catalysts provide the 2,3-epoxides in moderate to high enantioselectivity via the oxidation of the relatively electron-deficient double bond.

Continuous and convergent access to vicinyl amino alcohols.

Five active pharmaceutical ingredients (APIs) containing the vicinyl amino alcohol moiety were synthesized using a convergent chemical assembly system. The continuous system is composed of four flow reaction modules: biphasic oxidation, Corey-Chaykovsky epoxidation, phenol alkylation, and epoxide aminolysis. Judicious choice of reagents and module order allowed for two classes of ß-amino alcohols, aryl and aryloxy, to be synthesized in good (27-69%) overall yields.

Molecular iodine catalyzed cross-dehydrogenative coupling reaction between two sp3 C-H bonds using hydrogen peroxide.

A useful method for molecular iodine catalyzed oxidative C-C bond formation between tertiary amines and a carbon nucleophile using hydrogen peroxide as the terminal oxidant is reported. This is the first report of a molecular iodine catalyzed cross-dehydrogenative coupling (CDC) reaction between two sp(3) C-H bonds.

Direct aerobic photo-oxidative syntheses of aromatic methyl esters from methyl aromatics using anthraquinone-2,3-dicarboxylic acid as organophotocatalyst.

This paper reports a useful method for facile direct syntheses of aromatic methyl esters from methyl aromatics by aerobic photo-oxidation using anthraquinone-2,3-dicarboxylic acid as an organophotocatalyst.

One-pot metal-free syntheses of acetophenones from styrenes through aerobic photo-oxidation and deiodination with iodine.

A one-pot synthetic protocol of acetophenones from styrenes with molecular oxygen, visible light, and molecular iodine is reported. This procedure involves aerobic photo-oxidation and deiodination in one pot and provides the first report of metal-free direct syntheses of acetophenones from styrenes.

Direct aerobic photo-oxidative synthesis of aromatic methyl esters from methyl aromatics via dimethyl acetals.

A useful method for facile synthesis of aromatic methyl esters from methyl aromatics via dimethyl acetals by aerobic photo-oxidation using inexpensive and easily handled CBr(4) as catalyst is reported. This is the first example for direct preparation of the corresponding aromatic methyl esters from methyl aromatics.