Synthesis of fluorinated analogs of myristic acid as potential inhibitors of egyptian armyworm (Spodoptera littorialis) Δ¹¹ desaturasedesaturase

Abstract

To study the activity of the different desaturases present in the pheromone biosynthetic pathway of the Egyptian armyworm, Spodoptera littoralis, we prepared a series of mono- and gem-difluorinated analogs of myristic acid with halogen substitution at the C8-C11 positions of the aliphatic chain via specifically positioned dithiane precursors. Thus, transformation of dithianes by treatment with N-bromosuccinimide in the presence of H2O followed by reduction with LiAlH4 afforded the appropriate alcohols, which reacted with diethylaminosulfur trifluoride to give rise to the corresponding monofluoroderivative intermediates. Alternatively, the introduction of the gem-difluoro functionality was carried out by reaction of the appropriate dithiane intermediate with 1,3-dibromo-5,5-dimethylhydantoin in the presence of HF/pyridine. The activity of these fluorinated FA as substrates and inhibitors of the desaturases involved in the biosynthesis of the sex pheromonal blend of S. littoralis has been studied. In this case, 11-fluorotetradecanoic acid elicited a moderate inhibitory activity of delta11 desaturase.

Biosynthetic pathways of the pheromone of the Egyptian armyworm Spodoptera littoralis

“…It is widely known that fluorine atom closely mimics the steric requirement of hydrogen at enzyme receptor sites but its strong electronegativity significantly alters the reactivity of neighbouring centres (Ojima et al , 1996; Renou & Guerrero, 2000; Jeschke, 2004). In this context, Abad et al (2003) prepared a series of mono‐ and gem ‐difluorinated analogues of myristic acid with the halogen occupying the C8‐C11 positions of the aliphatic chain. None of the compounds was converted by the Δ11 desaturase of S. littoralis pheromone gland and only 11‐fluorotetradecanoic acid elicited a moderate inhibitory activity.…”

Synthesis and properties of monofluorinated dimyristoylphosphatidylcholine derivatives: Potential fluorinated probes for the study of membrane topology

“…Removal of the benzyl group 20 followed by oxidation of the newly revealed alcohol using TEMPO gave compound 2c in 77% yield. 20 Finally, the fluorinated fatty acid 2c is coupled with 1-myristoyl-2-hydroxy-sn-glycero-3-phosphocholine (lyso-PC) to give pure 10F-DMPC (1c) after purification by flash chromatography on silica gel using a 1 : 1 MeOH/CH 2 Cl 2 mixture as the eluent. An overall yield of 19% was obtained for the 7 synthetic steps.…”

Ni-Catalyzed Site-Selective Hydrofluoroalkylation of Terminal and Internal Olefins

“…This result tacitly illustrates the potential of light olefin feedstocks to rapidly and reliably homologate alkyl side chains by incorporating monofluorinated backbones. This observation was further assessed by accessing 25 an intermediate en route to a known Δ desaturase inhibitorfrom the formal coupling of ethyl dec-9-enoate, propene, and CHFBr 2 (bottom).…”