Synthesis of a carba‐analog of S ‐palmitoyl‐coenzyme A, heptadecan‐2‐onyldethio‐CoA, and of S ‐Heptadecyl‐CoA; effective inhibitors of citrate synthase and carnitine palmitoyltransferase

The syntheses of long chain alkyl‐coenzyme A derivatives 1 and 2 are reported. Heptadecan‐2‐onyldethio‐CoA (1) a carba analog of S ‐palmitoyl‐CoA is obtained along with its 2′‐phosphate isomer 11 by the condensation of adenosine 2′,3′‐cyclic phosphate‐5′‐phosphoromorpholidate (10) with the in situ generated palmitoyldethio‐carbapantetheine phosphate (8a) . The cyclic phosphodiester produced upon hydrolysis yields a mixture of 3′‐phosphate 1 and 2′‐phosphate 11. S ‐Heptadecyl‐CoA (2) is obtained from the alkylation of CoA with heptadecyl iodide. Both the isomeric mixture ( 1 + 11 ) and compound 2 exhibit characteristics of non‐competitive inhibition with citrate synthase (K 1 = 6.0–7.5 · 10 −6 mol/I and 1.0–1.5 · 10 −6 mol/l, respectively) and characteristics of competitive inhibition with carnitine palmitoyltransferase ( K 1 = 1.35 · 10 −6 mol/l and 3.34 · 10 −6 mol/l, respectively).