Preparation of 9α‐Fluorinated Sesquiterpenic Drimanes and Evaluation of Their Antifeedant Activities

Abstract

The preparation of 9α‐fluoro analogues of both natural and unnatural drimane‐type sesquiterpenes is described. Their synthesis began with the initial preparation of methyl 8‐keto‐12‐nordriman‐11‐oate from β‐ionone and entailed the electrophilic fluorination of C‐9 for the stereoselective introduction of the fluorine atom. The drimane skeleton was completed from the intermediate 9α‐fluoro‐8‐keto‐12‐nordrimane system by means of different reactions at the C‐8 ketone carbonyl group, essentially Wittig methylenation, cyanohydrin formation or palladium‐catalysed carbonylation of the corresponding enol triflate. Further manipulation of the functionalization derived from these key reactions allowed the preparation, among others, of 9α‐fluorodrimanes, which are structurally and functionally related to albicanic acid, drimenin and olepupuane. Also described are the reactivities of some of the fluorine‐containing systems prepared and a comparative study of the antifeedant activities of a selection of 9α‐fluorodrimanes and the corresponding hydrogen analogues against several insect species with different feeding ecologies (Spodoptera littoralis, Myzus persicae and Rhopalosiphum padi), which revealed a significant increase in the antifeedant activities of some of the fluorinated drimane analogues.

Fluoro‐Carba‐Sugars are Glycomimetic Activators of the glmS Ribozyme

“…For the next step, a regioselective reduction of the epoxide had to be found. The epoxide opening represented a crucial step, because attempts from other groups to open an epoxide next to fluorine in a similar compound under multiple reaction conditions had failed . Our first approach, utilizing stoichiometric amounts of TiCp 2 Cl in the radical opening of the epoxide, gave only a complex mixture with low quantities of the desired product .…”

Selective fluorination of natural products

“…The preparation of fluorinated natural sesquiterpenoids based on the drimane system has been reported and has focused on the production of 9--fluoro derivatives 9-14. 20 Abad's group sought to prepare several fluorinated analogues of the drimane framework and investigate how these changes could affect their chemical properties and biological activity. Fluorinated albicanic acid 11 was prepared from the starting fluorodecalone 9 which underwent a Wittig methylenation to afford ,-unsaturated ester 10 (Scheme 6).…”

Seven New Drimane-Type Sesquiterpenoids from a Marine-Derived Fungus Paraconiothyrium sporulosum YK-03

“…Drimanes, a type of sesquiterpenoid with a bicyclic scaffold, are widely distributed in plants, liverworts, fungi and certain marine organisms (sponges), possessing diverse structural features [27,28] and extensive biological activities, such as antibacterial [29,30], antifungal [31,32], antiviral [29,33], cytotoxic [34,35], antifeedant [36,37], plant-growth [38,39], and so on. Natural rearranged drimanes only occurred with a 1,2 methyl shift from C-4 to C-3 [40].…”

“…In 2013, the first drimanic compound with an aromatic ring was synthesized [41], while a synthesized seco-drimanic compound was reported for the first time in 2016 [42]. Because of their interesting structural features and bioactivities, they have attracted increasing attention of biologists and chemists for further research [36,41,43].…”