LABELED AMINO ACIDS AS DIAGNOSTICS NEW SYNTHESIS

THE PROPOSED PROGRAM RELATES TO THE DEVELOPMENT OF A UNIVERSAL ONE-STEP APPROACH TO 1-CARBON-2-AMINO LABELING WITH ANY ISOTOPE OF CARBON OR NITROGEN INCLUDING STABLE ([13]C, [15]N), RADIO ([14]C), AND POSITRON-EMITTING NUCLIDES ([11]C, [13]N). GIVEN THE INCREASED INVOLVEMENT OF AMINO ACID TECHNOLOGY IN CANCER RESEARCH AND TREATMENT, THIS PROPOSAL IS PERTINENT TO THE DEVELOPMENT AND EVALUATIONOF SPECIAL MATERIALS FOR USE IN MEDICAL IMAGING. THE ADVANTAGES OF THE APPROACH INCLUDE CONSERVATION OF ISOTOPE (COST SAVINGS) AND SPEED IN SYNTHESIS, THE LATTER ATTRIBUTE BEING EXTREMELY IMPORTANT IN ROUTINE USE OF POSITRON- EMITTING NUCLIDES. THE MAJOR OBJECTIVE OF THE PROGRAM IS TOINVESTIGATE THE APPLICATION OF COBALT OCTACARBONYL CATALYZEDCARBONYLATION OF ALIPHATI ALDEHYDES IN THE PRESENCE OF ACETAMIDE TO GIVE DL-N-ACETYLAMINA ACIDS IN ONE STEP. SECONDARY OBJECTIVES INCLUDE DEMONSTRATION OF 60% REACTION YIELD, INCREASED PRODUCT PURITY, SHORTENED REACTION TIME, STARTING-MATERIAL RECOVERY FOR RECYCLING ISOTOPE, AND REACTION SCALE-UP CAPABILITY. THE MAJOR ADVANTAGES OF THE APPROACH ARE ITS INHERENT SPEED IN SYNTHESIS, HIGH YIELD ANDGENERAL APPLICABILITY. THE PROGRAM APPROACH IS TO DEMONSTRATE THE REACTION SEQUENCE BY THE PREPARATION OF DL-N-ACETYL LEUCINE([13]C-LABELED AND UNLABELED) AND ITS ENZYMATICALLY RESOLVED L-AMINO ACID. DEMONSTRATION OF A COST-EFFECTIVE RAPID SYNTHESIS OF L-AMINO ACIDS IS EXPECTED.THE REACTION INVESTIGATED, CALLED CARBONYLACETAMIDATION, SHOULD PROVE SUPERIOR TO THE CONVENTIONAL STRECKER SYNTHESISIN YIELD AND PRODUCT PURITY, A SPECIAL ADVANTAGE TO USERS OFHIGH-COST ISOTOPE AND SHORT HALF-LIFE POSITRON EMITTERS. ADDITIONALLY, THE BASIC REACTION SCHEME IS FLEXIBLE ENOUGH TO ACCOMMODATE MILLIGRAM UP TO MULTI-KILOGRAM UNIT SCALES OF OPERATION. IMMEDIATE APPLICATIONS OF THE SYNTHESIS ARE IN PREPARATION OF POSITRON-EMITTER LABELED MATERIALS FOR EMISSION TOMOGRAPHY AND OF STABLE ISOTOPE-LABELED MATERIALS FOR CLINICAL RESEARCH AND DIAGNOSTIC PROTOCOL VALIDATION.