STUDIES ON THE SYNTHESIS OF NODUSMICIN, . 1. PREPARATION OF ZYLOXY-10-HYDROXY-8-METHYLBICYCLO[4.4.0]DECAN-3-ON

Our first target on the way towards the synthesis of nodusmicin is the preparation of the title compound. Meso diol 1 is partially etherifie d, then oxidized to the enone. The sterically compressed structure of this compound is the rationale of the highly stereoselective introduct ion of the substituents. (CH3)2CuLi introduces the methyl group and th e enolate is captured as silylenol ether, which in turn is transformed to the alpha-hydroxyketone by OsO4. Reduction leads to the vicinal tr ans diol. Protection of the exo-hydroxy group is followed by treatment with sodium in ethanol. Via intramolecular nucleophilic addition, sub stitution and dechlorination the tetracyclic diketal 8 is formed. Afte r exchange of the protective groups and partial hydrolysis of the keta ls the tertiary alkohol is obtained with methyl Grignard reagent. Acid ic fragmentation yields the desired title compound.