ABSTRACT
2-Amino-2-deoxy glycosides constitute an integral part of a variety of antibiotics and other biologically important glycoconjugates. 1 2-Amino-2-deoxy sugars are the key building blocks in the chemical synthesis of such complex carbohydrates. Danishefsky and coworkers reported a two-step synthesis of protected 2-benzenesulfonamido-2-deoxy-α-d-glucopyranose (such as 3) through an initial iodonium di-sym-collidine perchlorate-mediated iodosulfonamidation of glycals with benzenesulfonamide followed by treatment of the resulting iodo derivative (such as 2) with triethylamine in presence of water in THF. 2 Both the intermediates have been meticulously exploited by them for the synthesis of oligosaccharides, 3 N-linked glycopeptides, 4 Globo-H cancer vaccine, 5 etc. Being a hemiacetal, compound 3 offers additional scope for explorations towards the synthesis of nitrogen-containing heterocycles and carbocycles through reductive ring opening, followed by intramolecular ring closure reactions. Through this strategy, compound 3 has been successfully utilized by us for the synthesis of a few biologically important molecules, such as polyhydroxypyrrolidines, 6 l-gulonojirimycin, 7 steviamine analogues, 8 azanucleosides, 9 conduramine, aminocyclitols, azepanes, 10 etc. During the course of our research, we have identified N-iodosuccinimide (NIS) as a readily available and easy-to-handle alternative reagent to iodonium di-sym-collidine perchlorate. 6 Moreover, since the byproduct succinimide is soluble in water, we have been able to isolate compound 2 in pure form, simply by crystallization after work-up. Conversion of iodo sulfonamide derivative 2 to the 2-amino glycoside 3 was conveniently achieved using Danishefsky’s protocol and the product 3 was isolated directly by crystallization, thus making the two-step process, from 1 to 3, chromatography free. Subsequently, through the use of NIS in the first step, we were also able to synthesize hemiacetal 3 from 1 without isolating the intermediate 2 (Method B), and, in this case, the overall yield of the product 3 was found to be even higher than through the step-wise process. Method B is amenable for large-scale synthesis, as well; it has been tested with 20 g of 1.
