Synthesis of deuterated cyclopropene fatty esters structurally related to palmitic and myristic acids

Abstract

AbstractTo develop a synthesis of tritiated cyclopropene fatty acids (CPFA), compounds that should prove useful for affinity labeling of desaturases in insect pheromone biosynthetic studies, a series of novel, selectively deuterated CPFA analogues was prepared and characterized. In methyl [16‐2H]12,13‐methylene‐12‐hexadecenoate, the incorporation of deuterium was achieved by treatment of the corresponding ω‐chloro derivative with sodium borodeuteride in dimethylsulfoxide at 70°C for 24 h (67% yield) following conventional procedures. Alkylation of the tetrahydropyranyl derivative of 13‐tridecynol in the presence of lithium diisopropylamide in tetrahydrofuran at −20°C with 1‐chloro‐3‐iodopropane in hexamethylphosphoramide, followed by Jones oxidation of the crude product, yielded 16‐chloro‐12‐hexadecynoic acid (54%), which was esterified to the corresponding methyl ester by treatment with potassium carbonate and methyl iodide in dimethylformamide. Treatment of this acetylenic ester with ethyldiazoacetate in the presence of activated copper‐bronze as catalyst followed by hydrolysis in KOH solution at room temperature yielded 16‐chloro‐12,13‐(carboxymethylene)‐12‐hexadecenoic acid. This diacid was treated with excess oxalyl chloride to give the corresponding diacyl chloride, which was decarbonylated in a diethyl ether solution with zinc chloride, and the cyclopropenium ions thus formed were added at −40°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 prepare methyl [17‐2H]10,11‐methylene‐10‐hexadecenoate, methyl [17‐2H]11,12‐methylene‐11‐hexadecenoate and methyl [17‐2H]12,13‐methylene‐12‐hexadecenoate from the corresponding diacids using sodium borodeuteride in the reduction of the cyclopropenium ions. Alternatively, methyl [2,2,3,3‐2H4]hexadecynoate, prepared by reaction of methyl 2,11‐hexadecadiynoate with magnesium in deuterated methanol at room temperature, was submitted to the above cyclopropenylation and reductive decarbonylation sequence to give methyl [2,2,3,3,17‐2H5]‐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 developed. The methods should easily be applicable to the preparation of the corresponding tritiated analogues.