IRON COMPLEXES TO POLYENE SYNTHESIS

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The lone range goal of our research is to develop new synthetic methodology for the construction of C-C bonds in a stereospecific fashion. In particular, we wish to utilize the ability of a tricarbonyliron adjunct [Fe (CO)3] to: a) to control the stereochemistry of conjugated double bonds; b) to protect and stabilize labile and highly conjugated systems; c) to control the relative stereochemistry at asymmetric centers adjacent and remote to the coordinated diene. As vehicles for demonstration of this methodology, we have chosen macrolactin A, protomycinolide IV and the C9-Cl6 segment of ambruticin as targets. Macrolactin A is a 24-membered cyclic polyene lactone isolated from a taxonomically unidentified deep sea bacterium. This compound is active in inhibiting Herpes simplex viruses (I and II, ca. 7 ug/mL level) and in protecting T-lymphoplast cells against human immunosuppressive virus (HIV) replication (10 ug/mL level). The structure of this compound was determined via means of spectroscopic and degradation studies. Fermentation of this bacterium has proved to be unreliable, and thus larger quantities of macrolactin A are not available. Protomycinolide IV is a l6-membered cyclic polyene lactone possessing antibiotic properties against Gram positive bacteria. Ambruticin is a polyene impound isolated from the fermentation extracts of Polyangium cellulosum var. fulvum. It has exhibited unprecedented oral in vivo activity against systemic fungal infections histoplasmosis and cocidiomycosis.