Synthesis of (9Z,12E)- and (9E,12Z)-[1-14C]linoleic acid and (5Z,8Z,11Z,14E)-[1-14C]arachidonic acid

Article abstract of DOI:10.1016/0009-3084(95)02486-3

(3Z,6E)-1-Bromododeca-3,6-diene, a common intermediate in the synthesis of labelled 12t linoleic acid and 14t arachidonic acid, was obtained from (E)-3-nonyl-1-ol: in four steps, via conventional functional manipulations. Cross-coupling of this bromododecadiene with the Grignard reagent of 1-chloro-5-(tetrahydropyranyloxy)pentane gave a C17 dienic ether which was further transformed in three steps to 12t-[l-¹⁴C]linoleic acid in 22% overall yield from 3-nonyl-1-ol (eight steps). The synthesis of 14t arachidonic acid involves a Wittig reaction between (Z)-7-(t-butyldiphenylsilyloxy)hept-3-enal and the ylide of (3Z,6E)-dodeca-3,6-dienyl-triphenylphosphonium bromide. The resulting C19 tetraenic ether was transformed in three steps to 14t [l-¹⁴C]arachidonic acid (isomeric and radiochemical purities > 99%). 9t Linoleic acid was obtained by a stepwise six-carbon elongation chain of both ends of(E)-6-(2-tetrahydropyranyloxy)-hex-3-enyltriphenylphosphonium salt in 20% overall yield.