Studies toward the synthesis of durhamycins A and B and ziracin

Detailed in the following thesis are synthetic approaches toward the anti-HIV aureolic acids durhamycins A and B and the G-H orthoester of the oligosaccharide antibiotic ziracin.;With regard to the G-H orthoester of ziracin, the development of an efficient and kinetically driven route of spiro alpha-hydroxyorthoesters was required. The feasibility of an intramolecular nucleophilic trapping of epoxy ketene acetals was first examined. However, this strategy was abandoned due to the instability of the epoxy ketene acetal intermediates. A radical oxidation approach was then pursued and was found to work well for the formation of a simple spiro alpha-alkoxyorthoester. Ultimately, this approach was not pursued any further due to literature data that suggests the potential difficulties of applying this orthoesterification methodology to a complex oligosaccharide system.;A concise synthetic route towards durhamycins A and B, which could be readily adapted to analog synthesis, was pursued. Initially, an approach using a late-stage installation of the C(3) sidechain via the coupling of a cyclic allyl silane to a dimethyl acetal was targeted. After difficulty was encountered along this route, we revised our route so that a delta-alkoxy allyl borane species would be used to amend the C(3) sidechain to the naphthalene core of the aglycone. This strategy eventually led to the synthesis of a model compound that closely resembles the aureolic acid aglycone. Thus, a synthesis of the functionalized naphthalene portion of the aglycone was required in order to complete the synthesis of durhamycins A and B. And so, a [4+2] Diels-Alder/aldol strategy was attempted for the synthesis of the naphthalene core, but it was ultimately too inefficient. The current [4+2] benzyne strategy has shown more promise as a better synthetic route to the naphthalene core, however this study remains incomplete.