The stereoselective total synthesis of (+)-stagonolide B

The stereoselective total synthesis of the nonenolide, (+)-stagonolide B is described. The key steps involve epoxide homologation, hydrolytic kinetic resolution and ring-closing metathesis

Rationally Designed Pyrimidine Compounds: Promising Novel Antibiotics for the Treatment of <i>Staphylococcus aureus</i>-Associated Bovine Mastitis

Staphylococcus aureus is one of the major pathogens causing bovine mastitis, and antibiotic treatment is most often inefficient due to its virulence and antibiotic-resistance attributes. The development of new antibiotics for veterinary use should account for the One Health concept, in which humans, animals, and environmental wellbeing are all interconnected. S. aureus can infect cattle and humans alike and antibiotic resistance can impact both if the same classes of antibiotics are used. New effective antibiotic classes against S. aureus are thus needed in dairy farms. We previously described PC1 as a novel antibiotic, which binds the S. aureus guanine riboswitch and interrupts transcription of essential GMP synthesis genes. However, chemical instability of PC1 hindered its development, evaluation, and commercialization. Novel PC1 analogs with improved stability have now been rationally designed and synthesized, and their in vitro and in vivo activities have been evaluated. One of these novel compounds, PC206, remains stable in solution and demonstrates specific narrow-spectrum activity against S. aureus. It is active against biofilm-embedded S. aureus, its cytotoxicity profile is adequate, and in vivo tests in mice and cows show that it is effective and well tolerated. PC206 and structural analogs represent a promising new antibiotic class to treat S. aureus-induced bovine mastitis

Synthesis and Characterization of a Phosphate Prodrug of Isoliquiritigenin

Isoliquiritigenin (<b>1</b>) possesses a variety of biological activities in vitro. However, its poor aqueous solubility limits its use for subsequent in vivo experimentation. In order to enable the use of <b>1</b> for in vivo studies without the use of toxic carriers or cosolvents, a phosphate prodrug strategy was implemented relying on the availability of phenol groups in the molecule. In this study, a phosphate group was added to position C-4 of <b>1</b>, leading to the more water-soluble prodrug <b>2</b> and its ammonium salt <b>3</b>, which possesses increased stability compared to <b>2</b>. Herein are reported the synthesis, characterization, solubility, and stability of phosphate prodrug <b>3</b> in biological medium in comparison to <b>1</b>, as well as new results on its anti-inflammatory properties in vivo. As designed, the solubility of prodrug <b>3</b> was superior to that of the parent natural product <b>1</b> (9.6 mg/mL as opposed to 3.9 μg/mL). Prodrug <b>3</b> as an ammonium salt was also found to possess excellent stability as a solid and in aqueous solution, as opposed to its phosphoric acid precursor <b>2</b>