SYNTHESIS OF DEUTERATED CYCLOPROPENE FATTY ESTERS STRUCTURALLY RELATED TO PALMITIC AND MYRISTIC ACIDS

To develop a synthesis of tritiated cyclopropene fatty acids (CPFA), c ompounds that should prove useful for affinity labeling of desaturases in insect pheromone biosynthetic studies, a series of novel, selectiv ely deuterated CPFA analogues was prepared and characterized. In methy l [16-H-2]12,13-methylene-12-hexadecenoate, the incorporation of deute rium was achieved by treatment of the corresponding omega-chloro deriv ative with sodiun borodeuteride in dimethylsulfoxide at 70 degrees C f or 24 h (67% yield) following conventional procedures. Alkylation of t he tetrahydropyranyl derivative of 13-tridecynol in the presence of li thium diisopropylamide in tetrahydrofuran at -20 degrees C with 1-chlo ro-3-iodopropane in hexamethylphosphoramide, followed by Jones oxidati on of the crude product, yielded 16-chloro-12-hexadecynoic acid (54%), which was esterified to the corresponding methyl ester by treatment w ith potassium carbonate and methyl iodide in dimethylformamide. Treatm ent of this acetylenic ester with ethyldiazoacetate in the presence of activated copper-bronze as catalyst followed by hydrolyrsis in KOH so lution at room temperature yielded 16-chloro-12,13-(carboxymethylene)- 12-hexadecenoic acid. This diacid was treated with excess oxalyl chlor ide to give the corresponding diacyl chloride, which was decarbonylate d in a diethyl ether solution with zinc chloride, and the cyclopropeni um ions thus formed were added at -40 degrees C to a methanolic sodium hydroxide solution of sodium borohydride to give methyl 16-chloro-12, 13-methylene-12-hexadecenoate. Analogous procedures were followed to p repare methyl [17-H-2]10,11-methylene-10-hexadecenoate, methyl [17-H-2 ]11,12-methylene-11-hexadecenoate and methyl [17-H-2]12,13-methylene-1 2-hexadecenoate from the corresponding diacids using sodium boredeuter ide in the reduction of the cyclopropenium ions. Alternatively, methyl [2,2,3,3-H-2(4)]hexadecynoate, prepared by reaction of methyl 2,11 he xadecadiynoate with magnesiun in deuterated methanol at room temperatu re, was submitted to the above cyclopropenylation and reductive decarb onylation sequence to give methyl [2,2,3,3,17-H-2(5)]-11,12-methylene- 11-hexadecenoate. In summary, complementary methods for the selective incorporation of one to five deuterium atoms into cyclopropene fatty acids, at different sites, in moderate to high yields have been develo ped. The methods should easily be applicable to the preparation of the corresponding tritiated analogues.