Large-scale preparation of (9Z,12E)-[1-C-13]-octadeca-9,12-dienoic acid, (9Z,12Z, 15E)-[1-C-13]-octadeca-9, 12,15-trienoic acid and their [1-C-13] all-cis isomers

Several grams of labelled trans linoleic and linolenic acids with high chem ical and isomeric purities (> 97%) have been prepared for human metabolism studies. A total of 12.5 g of (9Z,12E)-[1-C-13]-octadeca-9,12-dienoic acid and 6.3 g of (9Z,12Z,15E)-[1-C-13]-octadeca-9,12,15-trienoic acid were obta ined in, respectively: seven steps (7.8% overall yield) and 11 steps (7% ov erall yield) from 7-bromo-heptan-1-ol. The trans bromo precursors used for the labelling were synthesised by using copper-catalysed couplings. The tra ns fatty acids were then obtained via the nitrile derivatives. A total of 2 3.5 g of (9Z,12Z)-[1-C-13]-octadeca-9,12-dienoic acid and 10.4 g of (9Z,12Z ,15Z)-[1-C-13]-octadeca-9,12,15-trienoic acid were prepared in five steps i n, respectively, 32 and 18% overall yield. Large quantities of bromo and ch loro precursors were synthesised from the commercially available acid accor ding to Barton's procedure. In all cases, the main impurities ( > 0.5%) of each labelled fatty acid have been characterised. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.