INEXPENSIVE PATHWAYS FOR THE SYNTHESIS OF BORONOPHENYLALANINE AND NEW BORON CONTAINING AGENTS

BORON NEUTRON CAPTURE THERAPY (BNCT) HAS A CLEAR THEORETICALADVANTAGE OVER OTHER TECHNIQUES AS A METHOD OF DELIVERING CELL-KILLING RADIATION TO CANCEROUS TUMORS. COMPOUNDS CONTAINING THE ELEMENT BORON, SUCH AS BORONOPHENYLALANINE (BPA), CAN ALSO SELECTIVELY LOCALIZE IN SKIN CANCERS SUCH ASMALIGNANT MELANOMA. UPON IRRADIATION BY A THERMAL OR EPITHERMAL NEUTRON BEAM, THE COMPOUND PRODUCES LOCALIZED RADIATION OF ONLY ONE OR TWO CELL WIDTHS THAT KILLS CANCER CELLS WITHOUT DAMAGE TO HEALTHY TISSUE AND BLOOD. BPA IS CURRENTLY USED IN CLINICAL NONRADIATION DOSAGE STUDIES IN THE U.S. FOR BNCT UNDER FDA INVESTIGATIONAL NEW DRUG STATUS. BPA IS BEING USED SUCCESSFULLY IN BNCT CLINICAL TRIALS IN JAPAN FOR THE TREATMENT OF MALIGNANT MELANOMA. INEUROPE AND AUSTRALIA, INTENSIVE INVESTIGATION OF BPA IS ONGOING. THE L-ISOMER OF BPA IS PREFERENTIALLY LOCALIZED INTUMORS AND SKIN CANCERS. CURRENT PROCESSES FOR PREPARATION OF L-(10)BPA, THE BORON-10 ENRICHED FORM DESIRED FOR BNCT, CONSIST OF MANY LABORATORY STEPS THAT ARE NOT ONLY COSTLY AND LABOR INTENSIVE, BUT PRODUCE A LOW YIELD OF BORON-TEN ENRICHED PRODUCT. THIS PHASE I PROJECT IS CONCERNED WITH NEW SYNTHETIC PROCEDURES DESIGNED TO PRODUCE L-(10)BPA IN A COST-EFFECTIVE PROCESS. THE NEW PROCESS WOULD MAKE L-(10)BPA READILY AVAILABLE AT AN AFFORDABLE COST SO AS TO MAXIMIZE R&D EXPENDITURES AND PROVIDE SUFFICIENT QUANTITIES FOR PRECLINICAL AND CLINICAL USE.