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

✍ Scribed by Ciardelli, Thomas ;Stewart, Charles J. ;Seeliger, Annemarie ;Wieland, Theodor

• Publisher: John Wiley and Sons
• Year: 1981
• Tongue: English
• Weight: 839 KB
• Volume: 1981
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.198119810508

✦ Synopsis

Abstract

The syntheses of long chain alkyl‐coenzyme A derivatives1 and2 are reported. Heptadecan‐2‐onyldethio‐CoA**(1)** a carba analog of S‐palmitoyl‐CoA is obtained along with its 2′‐phosphate isomer11 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′‐phosphate1** 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 compound2 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).