The aim of this proposal is to design an enantioselective synthesis of Chrysomycin B, an antitumor antibiotic which has the ability to intercalate DNA. A procedure has been developed for the synthesis and functionalization of various 2,6-substituted-5,6-dihydropyrans. These derivatives will be converted into the C-aryl glycoside of Chrysomycin B. The key annulation reaction to form the pyranose ring will involve the cyclization of a vinylsilane or an acetylene onto an oxonium cat ion. Functionalization of the resultant dihydropyran will be achieved by an allylic oxidation, which should allow for the stereoselective construction of the remaining hydroxylated portion of the G-aryl glycoside subunit. Once the glycoside of the Chrysomycins has been synthesized, the defucogilvocarcin aglycone will be constructed utilizing an established Suzuki arylation strategy. Not only is this synthetic strategy a de novo route to complex carbohydrate systems, but it is also comparable in length and convergency to the only known synthesis of the C-aryl glycoside of Chrysomycin B.
