Chemistry and inhibitory activity of long chain fatty acid oxidation of emeriamine and its analogues.
Emericedins A, B, and C, new betaines having inhibitory activity of long chain fatty acid oxidation, were isolated from the culture broth of Emericella quadrilineata IFO 5859. Their structures were determined by spectroscopic analyses as (R)-3-(acylamino)-4-(trimethylammonio)butyrate (acyl: A, acetyl; B, propionyl; C, n-butyryl). Structural confirmation and assignment of absolute configuration were made by chemical synthesis from L-asparagine. Deacylation of emericedin gave a potent derivative, (R)-3-amino-4-(trimethylammonio)butyrate, designated as emeriamine. In order to study the structure-activity relations, various analogues of emeriamine, including a stereoisomer, were prepared. Among them, N-palmitoyl and N-myristoyl derivatives showed much stronger inhibition of fatty acid oxidation than emeriamine.
D000818:Animals; D001622:Betaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002331:Carnitine; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D055598:Chemical Phenomena; D002621:Chemistry; D005227:Fatty Acids / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D005227:Fatty Acids; D001622:Betaine; C045761:emeriamine; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine