Retinoids (vitamin A), besides playing pivotal roles in the visual process as well as in the function of the purple membrane (the proton pump of Halobacterium halobium), has recently been shown to be potentially useful as chemotherapeutic agents in cancer and in skin disorders such as acne. The heart of the proposal concerns the synthesis of structurally and geometrically isomeric allenic retinoids and their rearrangement to retinoid analgoues via [l,j]-sigmatropic hydrogen shifts or other kinds of allylic rearrangements. The synthetic targets after rearrangement include sterically hindered geometric isomers as well as conformationally locked, double bond shifted or methyl substituted retinoids. The possible conversion of the Diels-Alder adduct of vitamin A acetate to hindered geometric isomers of retinal will also be investigated. As synthetic goals are achieved, structural and photophysical properties and the opsin binding ability of the various analogues will be examined as a means of understanding the structure of rhodopsin, bathorhodopsin and other species associated with the visual cycle. Finally, based on preliminary results, new studies regarding the electrocyclization of certain diene-allenes will be examined. In order to establish the scope of this methodology, drimane derivatives obtained from Beta-ionone by this novel method are proposed as precursors to (plus/minus)-widrol and optically active warburganal.
