Studies in asymmetric synthesis: Development of new synthetic methods for syntheses of natural products.

Abstract

The research, to be discussed in three chapters, involves the development of new synthetic methods which are applicable to the total synthesis of many natural products. Chapter 1: As a part of a program to synthesize new auxiliary agents for asymmetric synthesis, we have prepared a structurally rigid acetal from norbornene in three chemical steps. This enantiomerically pure acetal has been used for resolution of racemic α-hydroxy esters and might be applied as a chiral auxiliary for diastereoselective reactions. Chapter 2: The Calicheamicin and Esperamicin antibiotics have shown remarkable biological activity as site-specific cleaving agents of double stranded DNA. The oligosaccharide portion of these molecules plays an important role in the site specificity. We have developed synthetic methodologies that allow synthesis of the deoxyaminosugar components of these antibiotics and can be extended to synthesize unnatural amino sugars for structure-activity studies. Chapter 3: Enantiomerically pure cyclopropyl ketones, which are available via chiral ketals, are very useful for syntheses and diastereoselective manipulations of common and large rings. This method has been extended to introduce up to four contiguous chiral centers in a common ring. This extension could be useful for the syntheses of complex natural products.