Jesse M. Nicholson

Mammalian tyrosinase: isolation by a simple new procedure and characterization of its steric requirements for cofactor activity.

Abstract A method for the isolation of tyrosinase is described, which involves preparative polyacrylamide gel electrophoresis, requires only 24 to 36 h to carry out, and yields ostensibly homogeneous enzyme. The ability of purified tyrosinase to utilize 3,4-dihydroxyphenylalanine (dopa) analogs as cofactors was determined for both of the reactions catalyzed by tyrosinase: (i) tyrosine hydroxylation and (ii) dopa oxidation and melanin formation. The cofactor analogs studied included those in which steric modifying groups were added and those in which substitutions were made at the location of the amine, carboxylic acid, or hydroxyl groups of dopa. The results indicate that each of these groups is essential for maximal enzyme activity and that each is optimally located for tyrosinase activation when in the precise steric conformation found in l -dopa.

Enantioselective synthesis of 2-fluoro carboxylic acids from Trichloromethyl carbinols: an efficient approach to chiral fluorine introduction into insect sex pheromones

Abstract Chiral syntheses of 2-fluoro carboxylic acids were achieved (ee ≥ 92%, yield 50–60%) by stereoselective conversion (with inversion of configuration) of optically active trichloromethyl carbinols to fluoroacids with tetrabutylammonium fluoride. Fluorinated pheromone analogs of the European corn borer, Ostrinia nubilalis , and of the beet armyworm, Spodoptera exigua , were synthesized.

A sex attractant for the Siberian moth Dendrolimus superans sibiricus (Lepidoptera: Lasiocampidae).

Field trapping experiments were conducted against the Siberian moth, Dendrolimus superans sibiricus Butler, in Siberia, Russia, using traps baited with a virgin female moth or 100 μg synthetic mixtures of C12 straight chain-length aldehydes, alcohols, and acetates alone or in combinations on rubber septa. Traps baited with a 1:1 blend of aldehydes and alcohols captured many males. The capture rate was similar to the rate of capture seen in traps baited with virgin females. The mixture of aldehydes and alcohols (64% Z,E-5,7-dodecadienal, 10% Z-5-dodecenal, 18% E-7-dodecenal, 8% E-6-dodecenal) and (64% Z,E-5,7-dodecadien-1-ol, 10% Z-5-dodecen-1-ol, 18% E-7-dodecen-1-ol, 8% E-6-dodecen-1-ol) can be used as a sex attractant to monitor endemic Siberian moth populations in Asia, and for surveillance and detection of the moth in countries where the insect might be accidentally introduced.

Synthesis and Evaluation of Amino Analogues of Valproic Acid

Valproic acid, an antiepileptic drug, is extensively metabolized in humans. Two putative metabolites, 2-n-propyl-3-aminopentanoic acid (3-aminovalproic acid, 3-amino-VPA; 2a) and 2-n-propyl-4-aminopentanoic acid (4-amino-valproic acid, 4-amino-VPA; 4a), which may result from the transamination of the respective keto acids 1a and 3a may explain the unusual extended seizure protection elicited by valproic acid. The title compounds were synthesized as their diasteriomeric ethyl esters 2b and 4b and submitted for anticonvulsant evaluation by the Antiepileptic Drug Development Program of the National Institute of Neurological and Communicative Disorders and Stroke. The results verified our hypothesis, as 4b was active in the subcutaneous pentylenetetrazol (scMet) evaluation at 30 mg/kg. Both compounds were highly toxic at 300 mg/kg.