Synthesis of [9-14C]nonanoic acid via 2-thienyl(14CH3)(cyano)cuprate and its oxidation by newborn piglet muscle strips.
To determine if newborn piglet muscle could oxidize propionyl-CoA formed by catabolism of odd-chain fatty acids, an odd-chain fatty acid labeled in the terminal three carbons was needed. The synthetic scheme described is based upon the displacement of a primary alkyl iodide, ethyl 8-iodooctanoate, by a [14C]methyl group via an activated 2-thienyl(14CHa)(cyano)cuprate intermediate, forming ethyl [9-14C]nonanoate. Ethyl [9-14C]nonanoate was hydrolyzed in 6 N KOH and [9-14C]nonanoic acid recovered by ion-exchange chromatography. The yield of [9-14C]nonanoic acid was 40%, based on the initial amount of [14C]methyl iodide. The cuprate and other precursors were commercially available or readily synthesized from available precursors. Mass spectroscopy of commercial and synthesized nonradioactive nonanoate determined an m/z of 159 for the product molecular ion, as expected. The 14C-labeled product phenacyl ester was found to cochromatograph in a C-18 reverse-phase HPLC system with similarly derivatized commercially obtained nonanoic acid. The synthesis should be generally applicable to labeling of compounds by displacement of primary alkyl iodides, where other reactive groups (e.g., carboxylic acid), if present, can be protected (e.g., converted to an ester). Muscle strips isolated from the triceps muscle of newborn piglets oxidized [9-14C]nonanoic acid to 14CO2. Newborn piglet muscle can oxidize propionyl-CoA produced during odd-chain fatty acid oxidation.
Tetrick
M A
MA
Department of Nutritional Sciences, University of Wisconsin, Madison 53706, USA.
Crenshaw
T D
TD
Benevenga
N J
NJ
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002250:Carbon Radioisotopes; D005227:Fatty Acids / Q000138:chemical synthesis*; D066298:In Vitro Techniques; D018482:Muscle, Skeletal / Q000378:metabolism*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D013552:Swine
C106698:2-thienyl(cyano)cuprate; D000214:Acyl Coenzyme A; D002250:Carbon Radioisotopes; D005227:Fatty Acids; D009942:Organometallic Compounds; C009061:propionyl-coenzyme A; C008776:pelargonic acid