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

Abstract

To 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.

Biosynthesis of fatty acids and related metabolites

“…A series of deuteriated and tritiated cyclopropene C,, and C,, fatty acids has recently been synthesised, for affinity labelling of insect pheromone desaturases. 190 A wide range of 68 Scheme 15 specifically deuteriated mono-and di-unsaturated fatty acid alcohols (and acetates) has been synthesised for investigation into the biosynthesis of pheromones by Lepidoptera. 19' Saturated and unsaturated 2-ketones occur in the ejaculatory bulbs of mature males of the mulleri subgroup of the Drosophila.…”

Inhibitory effect of 10,11‐methyl‐enetetradec‐10‐enoic acid on a Z9‐desaturase in the sex pheromone biosynthesis of Spodoptera littoralis

“…d31 16:Acid was purchased from Fluorochem Ltd. (Derbyshire, UK) and d314:Acid from IC Chemikalien (Munich, Germany). dsEll-14:Acid and 10-MTA were prepared in our laboratory as described previously (Martinez et al, 1990;Gosalbo et al, 1993).…”

Fatty acids, fatty acid analogues and their derivatives

“…348 Cyclopropene fatty acids have been synthesised from acetylenic intermediates using ethyl diazoacetate as the cyclopropenating agent,349,350 or by alkylation of the corresponding 1 -lithiocyclopropenes.35' Another new approach to cyclopropene fatty acids has been developed for the synthesis of methyl sterculate 40 and methyl 2-hydroxy-sterculate, which involved the 1,2-deiodination of 1,2-diiodocyclopropanes with butyllithium at low temperat~re.~'~ The synthesis of deuteriated cyclopropene fatty esters structurally related to palmitic and myristic acids has been reported. 353 A The racemic mixture of a cyclopentenone fatty acid 42 produced by duckweed, which inhibits algae growth, was synthesised by Michael addition of nitromethane to 2-methylcyclopent-2-enone followed by carbonyl protection and the Nef reaction to give an aldehyde which was further elaborated by Wittig reaction and reduction. The cyclopentenone double bond was subsequently introduced by selenat i ~n .…”