Kabita Pradhan

. Strikingly, these inhibitors acted in a bacteria-selective manner. These metabolic inhibitors will provide a platform for systematic study of bacterial glycosylation enzymes not currently possible with existing tools. Moreover, their selectivity will provide a pathway for the development of novel, narrow-spectrum antibiotics to treat infectious disease. Our inhibition approach is general and will expedite the identification of bacterial glycan biosynthesis inhibitors in a range of systems, expanding the glycochemistry toolkit.

Bacterial cell‐surface nonulosonic acids are unique in their structural complexity and their biological roles in life processes. Their presence at the non‐reducing end of bacterial cell surface glycans makes them key players in infections related to various multidrug‐resistant pathogens. These glycans are difficult to isolate from natural sources in pure form. Also, due to their complicated structures, access to these rare sugars through synthesis is highly challenging. The most well‐studied bacterial nonulosonic acid is pseudaminic acid which has been synthesized by many groups and reviewed very recently. In this minireview, we discuss the recent advances in the synthesis of remaining nonulosonic acids viz. legionaminic acid, acinetaminic acid, and fusaminic acid.

Herein we report the first total synthesis of a densely functionalized tetrasaccharide repeating unit of Vibrio cholerae O43, which contains rare deoxy amino sugars d-quinovosamine and d-viosamine attached with the rare amino acid N-acetyl-l-allothreonine. Synthesis of orthogonally protected rare sugars and unnatural amino acid building blocks, stereoselective construction of three consecutive 1,2-cis glycosidic linkages, amide coupling, and the presence of five nitrogen atoms dispersed over four sugar units as well as the carboxylic acid functionality make the total synthesis a formidable task.

Vibrio cholerae is a pathogen responsible for the deadly pandemic – cholera. The glycans present on the surface of various strains of V. cholerae are considered as potential vaccine candidates. The tetrasaccharide repeating unit (RU) of V. cholerae O43 is decorated with less-explored rare deoxy amino sugars like d-quinosamine and d-viosamine, along with a rare amino acid, N-acetyl-l-allothreonine. Herein, we report a detailed account of the total synthesis of V. cholerae O43 tetrasaccharide RU. In our earlier attempt, while a one-pot assembly of trisaccharide was successful, the final coupling with a fully functionalized d-viosamine donor was low yielding. The successful route involved employing the Fmoc-protected d-viosamine building block as a donor and a late-stage amide bond formation of the tetrasaccharide.

The Cover Feature shows the iconic “Infinity Corridor” of the Indian Institute of Technology Bombay. Metaphorically, it represents the ongoing efforts towards the synthesis of bacterial nonulosonic acids. The structurally complex nonulosonic acids are present at the termini of bacterial cell-surface glycoconjugates and thereby play key roles in pathogen-host interactions. In this review, we have summarized the biosynthetic, enzymatic or chemical approaches to access three types of nonulosonic acids viz. Legionaminic acid (Leg), Acinetaminic acid (Aci), and Fusaminic acid (Fus) from diverse starting materials. More information can be found in the Minireview by K. Pradhan and S. S. Kulkarni et al.