Development of Thermally and Photochemically Stable Anesthetic Components

"Low photo- and thermal stability of (R)-epinephrine (vasoconstrictor) in localanesthetic formulations compromises their anesthetic afficacy in field austereenvironments. The overall objective of this proposal (Phase I and Phase II combined)is to synthesize potentially stable vasoconstrictors, study their stability, andprove their anesthetic efficacy. Toward this end, Phase I focuses on the synthesisof ring-fluorinated analogs of (R)-epinephrine and (R)-phenylephrine using PoliumTechnologies proprietary biocatalyst, Finezyme-H1. Synthesis of chiral fluorinatedderivatives of (R)-phenylephrine by any methods has not been described. Publishedmethods of the synthesis of chiral fluorinated epinephrine derivatives use harshconditions that are difficult for the scale-up. Contrary to this, Finezyme-H1catalyzed reactions use mild conditions and the method is easily scaleable. Theliterature data suggest that these fluorinated analogs may possess requiredbiological properties. Phase I focuses on the synthesis of these compounds usingproprietary technology and stability studies of fluorinated analogs. If candidatecompounds synthesized during Phase I show higher stability than existingvasoconstrictors, during Phase II we will test these compounds in local anestheticformulations, perform biological affinity receptor assays and perform toxicologystudies. Successful candidates will be commercialized in DOD and private sector Many third world