I. Synthesis of new thio- and selenoglycosides towards glycomimetics and enzyme inhibition. II. Preparations and reactions of thio- and selenocarboxylates. III. Synthesis of mycothiol analogues

I. The synthesis of small carbohydrate derivatives that can act as inhibitors and glycomimics are of great importance to the understanding of structure and mechanism of enzymes involved in carbohydrate synthesis and hydrolysis. GlcNac-selenazoline 1-69 and the S-methyl thiazoline 1-98 have been synthesized as inhibitors of β-hexosaminidases. Hexosaminidases catalyze the cleavage of N-acetyl hexosamines from oligosaccharides and other glycoconjugates. The clinical disorders known as Tay-Sachs and Sandhoff disease stem from defects in human hexosaminidase enzymes.;Various new thioglycosides, including sulfonates, sulfenamides, and sulfonamides have been synthesized as potential glycomimics. Replacement of the linking oxygen of glycoconjugates with a sulfur atom provides the corresponding thioglycoside. The C-S bond's resistance to enzymatic cleavage and acid hydrolysis makes thioglycosides attractive as enzyme inhibitors and enzyme resistant substrates.;II. Thio- and selenocarboxylates can be generated in situ to provide acids that can react to give new products of acid- or base-promoted addition, substitution, and amidation reactions under mild conditions. The in situ generation of selenocarboxylic acids (2-21), for example, minimizes the formation of the corresponding diselenide, which is often problematic in the synthesis of selenol compounds. The organic solution of the acids can be used to introduce the sulfur and selenium atoms into a wide range of organic structures including amino acids and carbohydrates.;III. The simplified mycothiol analogue 3-14 proved to be a good substrate for the mycothiol conjugate amidase (Mca), the enzyme responsible for the cleavage of the cysteine derivative from mycothiol (MSH). The data indicated that the inositol ring and linking oxygen atom of MSH contribute little to substrate binding, and thus might be dispensed with in the design of inhibitors of Mca. As most of the enzymes in the mycothiol biosynthetic pathway involve attaching, cleaving, or maintaining an acyl group at the nitrogen of a 2-deoxy-2-amino-α-D-glucopyranoside, the thioglycoside aminotriol 3-13 seemed to be a promising starting point for the preparation of inhibitors. Aminotriol 3-13 was used as a scaffold for the synthesis of potential inhibitors of enzymes of the mycothiol biosynthetic pathway.