The principle objectives of the research program as set forth in this proposal are the development and execution of efficient asymmetric syntheses of the structural types found in the natural products castanospermine, deoxynojirimycin, and other glucosidase inhibitors, and oxetanocin, a novel oxetane-containing nucleosides with reverse transcriptase inhibitory activity. Members of these structurally distinct classes of compounds are being intensely scrutinized because of their anti- human immunodeficiency virus (HIV) activity. While we illustrate our strategy with syntheses of the natural compounds, our primary concern is with the definition of synthetic routes that are general enough so that the synthesis of analogs can be pursued directly, without the need to redesign the synthetic protocol for each new derivative. Thus, we expect that the generality of our synthetic approaches will allow for the facile production of new molecules structurally related to the target compounds (i.e., analogs), thereby enabling a better understanding of the relationship of chemical architecture and biological function. Certain analog syntheses are discussed in this proposal.
