This grant will continue a research program to investigate the fundamental chemistry of recently discovered, bioloically active natural products. Our plans include two major target areas for study. Firstly, our continuing efforts for synthesis of the pseudomonic acids A, B, and C are nearing completion. These studies have led to the development of efficient strategies for prepartion of L-carbohydrates and stereochemically complex oxacyclic systems. The major emphasis of this proposal describes strategies for highly convergent, enantiospecific investigations of the chemistry of the lankacidins. These unique macrocyclic metabolites display considerable antitumor activity against L1210 leukemia, B16 melanoma, and solid lymphosarcoma, in vivo, and are only weakly toxic in mice. They also show strong atimicrobial activities, principally against Gram-positive bacteria, including some strains of clinically resistant isolates.
