The antibiotics represent an extremely important class of biologically active molecules, some of which bear strong chemical and structural similarities to certain carbohydrates. This grant in the Organic and Macromolecular Chemistry Program is directed toward utilizing them as cheap and efficient starting materials for certain classes of antibiotics such as the streptovaricins. The general objective of this research program is to develop the efficient use of readily available carbohydrate derivatives in organic synthesis. The testing ground is the ansa chain of streptovaricin A. Two different approaches are described. The first, in progress, involves a process known as pyranosidic homologation in which the sugar is elaborated into a bi- and thence a tri-pyranose, whose continuous carbon backbone /provides the required number of stereogenic centers. The second approach is a convergent process, which plans to make use of a remarkable aldol condensation that has been uncovered in earlier work. The substrate, a 3-keto pyranoside, is itself remarkable in that it shows no inclination toward beta elimination. This unexpected stability is merely one of several idiosyncracies encountered in the course of these investigations, which reveal striking differences between carbohydrates and carbo-cycles that are not satisfactorily "explained" by current theories. A substantial effort is therefore directed toward a systematic investigation of these idiosyncracies, employing a combination of theoretical and experimental methods, buttressed by appropriate computer-assisted modelling techniques.
