A one-pot preparation of N-2-mercaptobenzoyl-amino amides

Abstract

The HIV-1 nucleocapsid (NCp7), structurally defined by zinc-binding domains, participates in crucial stages of the HIV-1 lifecycle and is mutationally nonpermissive, making it an attractive anti-HIV target. Mode of action studies have shown that the secondary structure and activity of NCp7 can be disrupted by acyl transfer from N-2-mercaptobenzoyl-amino amides. We have developed an improved one-pot reaction that affords N-2-mercaptobenzoyl-amino acids on multi-gram scales. This synthetic route allows for rapid modular construction and has greatly expanded the scope of easily accessible potential NCp7 inhibitors.

A fluorescent τ-probe: quantitative imaging of ultra-trace endogenous hydrogen polysulfide in cells and in vivo

“…The synthesis procedure of the τ -probe is shown in Scheme S1. † CH 2 Cl 2 (20 mL) was added to a mixture of 3- O -methylfluorescein 50 (69.2 mg, 0.2 mmol), 2-(benzoylthio)benzoic acid 37 , 51 (78 mg, 0.3 mmol), EDC (58 mg, 0.3 mmol) and DMAP (12.2 mg, 0.1 mmol) at room temperature and the mixture was stirred for 5 h. Then the solvent was evaporated under reduced pressure and the resulting residue was subjected to high performance liquid chromatography for purification. The τ -probe was obtained as a yellow solid.…”

Reaction Kinetics Direct a Rational Synthesis of an HIV‐1 Inactivator of Nucleocapsid Protein 7 and Provide Mechanistic Insight into Cellular Metabolism and Antiviral Activity

“…Topical microbicide and slow‐release formulations of 1 and related derivatives have shown significant promise in preventing HIV transmission in macaque models . As such, 1 is an ideal candidate for further preclinical evaluation; however, the lack of an efficient synthesis (Scheme S1 in the Supporting Information), as well as gaps in the basic understanding of how this molecule inhibits HIV maturation without toxicity, are both hindering preclinical development.…”

A novel preventive strategy against HIV-1 infection: combinatorial use of inhibitors targeting the nucleocapsid and fusion proteins

“…SAMT10 was synthesized as previously described. 20 A 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) powder was purchased from Thermo Fisher Scientific (Waltham, MA, USA), and nonoxynol-9 (N-9) was purchased from ScienceLab.com, Inc. (Houston, TX, USA). For in vitro cell experiments, MTT, N-9, and SFT were dissolved in sterile phosphate-buffered saline (PBS, pH=7.4) at the indicated concentrations.…”