Engineering of Nisin as a Means for Improvement of Its Pharmacological Properties: A Review.

Lantibiotics are believed to have a conceivable potential to be used as therapeutics, especially against clinically resistant bacterial strains. However, their low solubility and poor stability under physiological conditions limit their availability for clinical studies and further pharmaceutical commercialization. Nisin is a readily available and cheap lanthipeptide and thus serves as a good model in the search for the tools to engineer lantibiotics with improved pharmacological properties. This review aims to address technologies that can be applied to alter and enhance the antimicrobial activity, antibacterial spectrum and physicochemical properties (solubility, solution stability and protease resistance) of nisin. There are basically two general means to obtain nisin analogs-protein engineering and chemical functionalization of this antibiotic. Although bioengineering techniques have been well developed and enable the creation of nisin mutants of variable structures and properties, they are lacking spectacular effects so far. Chemical modifications of nisin based on utilization of the reactivity of its free amino and carboxylic moieties, as well as reactivity of the double bonds of its dehydroamino acids, are in their infancy.

Cobalt Catalyst Determines Regioselectivity in Ring Opening of Epoxides with Aryl Halides.

Ring-opening of epoxides furnishing either linear or branched products belongs to the group of classic transformations in organic synthesis. However, the regioselective cross-electrophile coupling of aryl epoxides with aryl halides still represents a key challenge. Herein, we report that the vitamin B12/Ni dual-catalytic system allows for the selective synthesis of linear products under blue-light irradiation, thus complementing methodologies that give access to branched alcohols. Experimental and theoretical studies corroborate the proposed mechanism involving alkylcobalamin as an intermediate in this reaction.

Convenient Synthesis of Functionalized Unsymmetrical Vinyl Disulfides and Their Inverse Electron-Demand Hetero-Diels-Alder Reaction.

The simple, convenient, and efficient methods for the preparation of unsymmetrical vinyl disulfides with additional functional groups under mild conditions with moderate to high yields were designed. The developed methods include the reaction of S-vinyl phosphorodithioate with thiotosylates or S-vinyl thiotosylate with thiols. The designed methods allow for the synthesis of unsymmetrical vinyl disulfides with additional functionalities such as hydroxy, carboxy, protected amino, or ester groups. Vinyl disulfides reacted with the generated transient o-iminothioquinones in an inverse electron-demand [4+2] cycloaddition to produce benzo[b][1,4]thiazine derivatives.

Convenient and Efficient Synthesis of Functionalized 2-Sulfenylindoles.

A simple, efficient, and practical sulfenylation at the C2 position of N-tosylindoles under mild conditions was developed. The designed transformation is based on the reaction of N-tosylindoles with BuLi and S-alkyl, and S-aryl phosphorodithioates or thiotosylates to produce 2-sulfenylindoles in moderate to high yields. The presence of additional hydroxy, carboxy, or amino functionalities did not disturb the formation of products.