This project undertakes the formulation of an improved synthesis of isofluorane, a commonly used general anesthetic. In addition to pathways that rely on resolution of enantiomers, enantiospecific synthetic transformations are proposed. Specific reactions to be explored include enantiospecific decarboxylation reactions, in which the putative carbanion is not resonance-stabilized. Direct asymmetric synthesis will be studied wherein fluorination of an oxazolidinone enolate will be carried out; alternatively, asymmetric protonation of a bis-silyl ketene acetal will be attempted. The ultimate goals of the proposal include a practical asymmetric synthesis of isofluorane, which will enable pharmacological studies into the chiral dependence of the anesthetic effect, as well as the provision of research opportunities at the Principal Investigator's predominantly undergraduate institution.
With this Award, the Organic and Macromolecular Chemistry Program (Organic Synthesis) extends support to CUNY Baruch College for the research being conducted by Professor Keith M. Ramig and his undergraduate students of chemistry. Professor Ramig is attempting to establish a practical method for the separate production of both individual forms of the commonly used general anesthetic isofluorane. Various chemical reactions will be attempted to find the most effective means of carrying out this procedure. Success in this endeavor will enable future studies into the pharmacology of anesthesia with a view to the exact way in which this important effect occurs.
