Naturally occurring compounds consisting of multiple olefinic sites occupy a special niche among physiologically active agents. Included in this polyene group are (1) the polyene macrolide antibiotics, clinically valued as anti-fungals. The ion channel-forming materials usually contain between four and seven E-olefins in a conjugated array. The use of conjunctive reagents for rapidly preparing oxo tetra- to heptaene subsections in stereochemically homogeneous form is to be pursued; (2) new routes to biaryls bearing axial chirality, in particular the biaryl portions of vancomycin and michellamine B, will be studied. The former is one of the world's last lines of defense against certain bacterial infections, and the latter is an especially effective anti-AIDS compound. Both targets will derive from an intra-molecular biaryl coupling strategy via organometallic intermediates. Stereoinduction will be controlled by the nature of the tether joining the individual aryl components. Thus, this application discusses not only considerable published progress made during the currant grant period, but extensive unpublished data in support of both the continuing and especially, the new directions in our polyene program, outlined herein. In amines, and (b) nickel-on-charcoal as an effective, inexpensive and environmentally benign catalyst for effecting C-C band formations which should assist us in reaching our goals, and provide general utility as well to the synthetic community.
