APPLICATIONS OF IRON COMPLEXES TO ORGANIC SYNTHESIS

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The long range goal of our research is to develop new synthetic methodology for the construction of C-C bonds in a stereospecific fashion. This new methodology will be useful for the preparation of polyene macrolides and for the preparation of cyclopropane containing natural products. In particular, we wish to utilize the ability of an ironcarbonyl adjunct: a) to control the stereochemistry of conjugated dienes and to protect the diene against reduction oxidation, and cycloaddition reactions; b) to control the relative stereochemistry at asymmetric centers adjacent and remote to a conjugated diene; c) to control the relative stereochemistry of trisubstituted cyclopropanes; d) to control the relative stereochemistry at asymmetric centers adjacent to a trans-disubstituted cyclopropane. As vehicles for demonstration of these methodologies, we have chosen macrolactin A, madumycin II, ambruticin, 2-(2'- carboxycyclopropyl) glycines, and FR-900848 as targets. Macrolactin A was isolated from an unidentified deep sea bacterium. This compound exhibits antiviral activity against Herpes Simplex I and II and against HIV in initial tests. Since the culturing of this bacterium has been "unreliable", further biological research must rely on total synthesis. Madumycin II is a member of the streptogramin A family of antibiotics which are active against Gram-positive organisms. Ambruticin is a structurally complex antifungal agent. This compound was found to be orally active against systemic infections of histoplasmosis and coccidiomycosis. Several 2-(2'-carboxycyclopropyl)glycines have been found to be potent ligands for metabotropic glutamate receptors. FR-900848 is a polycyclopropane molecule isolated from the fermentation of Streptoverticillium fevens which inhibits filamenteous fungi such as Aspergillus niger, but has relatively low toxicity in mammals (LD50 greater than 1g/1kg).