NOVEL PROCESS TO SYNTHESIZE (R)-CYANOHYDRINS

CHIRAL DRUGS ADMINISTERED IN ENANTIOMERICALLY PURE FORM OFFER SIGNIFICANT CLINICAL ADVANTAGES OVER THEIR RACEMIC COUNTERPARTS. HOWEVER, AVAILABLE METHODS TO PREPARE ENANTIONMERICALLY PURE COMPOUNDS HAVE DRAWBACKS, INCLUDING HIGH COST, LIMITS ON CHEMICAL AND ENANTIOMERIC PURITY, AND DIFFICULTY WITH PROCESS SCALE-UP. THE GOAL OF THIS PROJECT IS TO DEMONSTRATE THE FEASIBLITY OF A RELIABLE, ECONOMICAL PROCESS TO PREPARE ENANTIOMERICALLY PURE (R)-CYANOHYDRINS. CHIRAL CYANOHYDRINS ARE IMPORTANT SUBSTANCES LEADING TO SYNTHONS (E.G., AI-HYDROXYACIDS, BETA-AMINO ALCOHOLS, B-AMINO KETONES, AND AI-AMINO ACIDS), INTERMEDIATES USED TO PREPARE ENANTIOMERICALLY PURE DRUGS. IN PHASE I, WORK WILL BE FOCUSED ON PREPARING AN ENANTIOMERICALLY PURE CHIRAL CYANOHYDRIN THAT CAN BE USED TO PREPARE (R)-ALBUTEROL, AN IMPORTANT BRONCHIAL ASTHMA DRUG. SPECIFICALLY, WE PLAN TO DEMONSTRATE THAT THE PROCESS (1) IS TECHNICALLY FEASIBLE, (2) CAN PRODUCE (R)-ALBUTEROL AT AN ENANTIOMERIC PURITY SUFFICIENT FOR USE IN PHARMACEUTICAL PRODUCTION, AND (3) SHOWS PROMISE OF BEING ECONOMICAL AND SUITABLE FOR LARGE-SCALE PRODUCTION. SUCCESS IN PHASE I WOULD LEAD TO A PHASE II PROGRAM FOCUSED ON (1)CHARACTERIZING THE TECHNOLOGY (2) EXPANDING IT TO A WIDER RANGE OF CHIRAL CYANOHYDRINS, (3) DEVELOPING OPTIMIZATION STRATEGIES, (4) IDENTIFYING SCALE-UP TISSUES AND VALIDATING THE TECHNOLOGY AT THE 1 KG SCALE, AND (5) COMPLETING A DETAILED ECONOMIC ANAYLSIS,