The development of the novel concept of glycosyl transfer via cycloaddition chemistry is the intended outcome of the work proposed. Cycloaddition reactions will be developed for the synthesis of important glycoside linkage types including 2-deoxy-O (found in many antibiotics), 2.deoxy-N, 2-deoxy-2-amino-N, and 2-deoxy-2-mercapto-O (in the rare rhodocardins) among others. Different from the well-developed paradigm of glycosidation via electrophilic activation of the anomeric center followed by nucleophilic substitution, our method exploits heterocycloaddition for group transfer. The principles of our concept can be illustrated in the general scheme where a sugar dienophile undergoes highly stereoselective cycloaddition with heterodiene to afford adduct. Further, straightforward chemistry yields glycosides. In principle, our generalized glycosidation method involves chemistry that is benign towards essentially every blocking group used in glycosides and that is also benign for almost every functional group found in aglycones which might be coupled to sugars. Hence, our new scheme and its variations described in the proposal will be valuable for the stereoselective synthesis of important glycosides.
| Diep, Vinh; Dannenberg, J J; Franck, Richard W (2003) An o-iminothioquinone: its cycloaddition to produce an indologlycoside and its self-dimerization to form a dithio-diazocycloctane, the structure assignment of which is based on the DFT prediction of its IR spectrum. J Org Chem 68:7907-10 |
