This proposal describes new reactions and methods for the chemical synthesis of two general families of biologically significant glycoconjugates: (1) furanosyl and pyranosyl nucleosides, and (2) C- arylglycosides. The long term objectives are to develop new transition metal-mediated reactions for the efficient preparation of antitumor and antiviral carbohydrate-containing compounds. This proposal describes our continued work with molybdenum pentacarbonyl- mediated cycloisomerization reactions of alkynyl alcohols to endocyclic enol ethers (glycals) and specific application of this chemistry to anti- AIDS nucleosides such as dideoxynucleosides, the antineoplastic compound puromycin, and antifungal compounds such as polyoxin and amipurimycin. Our efforts will focus on extending the scope of the cycloisomerization to amide-containing alkynols, as well as extension to pyranosyl nucleosides. We will also study new postcyclization strategies for preparing nucleosides from glycals. This application also features the rhodium-catalyzed cyclotrimerization of alkynyl-carbohydrates. We propose application of this methodology to a short, direct synthesis of the antifungal drug papulacandin, as well as extending this approach to the angucycline antitumor antibiotic urdamycinone. We will also explore this methodology for the synthesis of C-arylglycoside compounds which have not yet been synthesized, such as ravidomycin as well as the bis-C-aryl glycoside, kidamycin.
|Balthaser, Bradley R; McDonald, Frank E (2009) Brønsted acid-promoted glycosylations of disaccharide glycal substructures of the saccharomicins. Org Lett 11:4850-3|