Synthesis of the namenamicin A-C disaccharide: towards the total synthesisof namenamicin

Progress towards the total synthesis of namenamicin (1), the only enediyne antitumor antibiotic of marine origin, is reported. Two methods were invest igated for the stereoselective introduction of the highly unusual quaternar y C-4 center of the A-ring. Spirocyclic [3,3]-sigmatropic rearrangements of the thiocarbonates 6 and 10 gave products 7 and 11, from processes involvi ng approach of the sulfur atom solely to the alpha-faces of the substrates, The desired stereochemistry of the quaternary center was ultimately obtain ed by way of an intramolecular Michael addition of a xanthate anion derived from the alpha,beta-unsaturated methyl ester 18. Further functional group manipulations provided an olefin 25 which underwent dihydroxylation to give a mixture of diastereomeric diols 26, allowing access to both potential di astereomers of the natural product. The A ring intermediate 29 was found to be a viable substrate of glycosidation with a glycosyl fluoride of the C r ing aminosugar 30, providing the protected A-C disaccharide subunit of 1.