Metalloenamine reactions: Synthesis of Halichlorine

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DESCRIPTION (provided by applicant): The majority of drug candidates are amine-containing compounds. Thus the development of new methods to make amines efficiently and stereoselectively is a continuing goal. The Ellman group has been exploring ways to generate amine compounds asymmetrically using readily available sulfinyl imines of simple aldehydes and ketones. They have recently reported the first use of these sulfinyl imines as nucleophiles by converting the imine into a metalloenamine, and then reacting them with aldehydes. This proposal plans to extend this metalloenamine chemisty and apply it to the formal synthesis of Halichlorine, a potential anti-inflammatory and anti-cancer agent. The synthesis involves adding these chiral metailoenamines to prochiral Michael acceptors in a conjugate fashion. This would allow for rapid chain extension and selective generation of multiple stereocenters from one chiral auxiliary. If successful, a diverse array of structural motifs found in many alkaloids can be constructed using this methodology.