Large-scale preparation of (9Z,12E)-[1-(13)C]-octadeca-9,12-dienoic acid, (9Z,12Z,15E)-[1-(13)C]-octadeca-9,12,15-trienoic acid and their [1-(13)C] all-cis isomers.
Several grams of labelled trans linoleic and linolenic acids with high chemical and isomeric purities (>97%) have been prepared for human metabolism studies. A total of 12.5 g of (9Z, 12E)-[1-(13)C]-octadeca-9,12-dienoic acid and 6.3 g of (9Z,12Z, 15E)-[1-(13)C]-octadeca-9,12,15-trienoic acid were obtained in, respectively, seven steps (7.8% overall yield) and 11 steps (7% overall yield) from 7-bromo-heptan-1-ol. The trans bromo precursors used for the labelling were synthesised by using copper-catalysed couplings. The trans fatty acids were then obtained via the nitrile derivatives. A total of 23.5 g of (9Z,12Z)-[1-(13)C]-octadeca-9, 12-dienoic acid and 10.4 g of (9Z,12Z,15Z)-[1-(13)C]-octadeca-9,12, 15-trienoic acid were prepared in five steps in, respectively, 32 and 18% overall yield. Large quantities of bromo and chloro precursors were synthesised from the commercially available acid according to Barton's procedure. In all cases, the main impurities (>0.5%) of each labelled fatty acid have been characterised.
Loreau
O
O
CEA/Saclay, Service des Molécules Marquées, Bât. 547, F-91191 Cedex, Gif sur Yvette, France. olivier.loreau@cea.fr
Maret
A
A
Poullain
D
D
Chardigny
J M
JM
Sébédio
J L
JL
Beaufrère
B
B
Noël
J P
JP
D002247:Carbon Isotopes; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D019787:Linoleic Acid / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D013237:Stereoisomerism; D017962:alpha-Linolenic Acid / Q000138:chemical synthesis* / Q000737:chemistry*
D002247:Carbon Isotopes; D017962:alpha-Linolenic Acid; D019787:Linoleic Acid