Optimization of Insecticidal Triterpene Derivatives by Biomimetic Oxidations with Hydrogen Peroxide and Iodosobenzene Catalyzed by Mn^III and Fe^III Porphyrin Complexes

Abstract

Semisynthetic functionalized triterpenes (4α,14‐dimethyl‐5α,8α‐8,9‐epoxycholestan‐3β‐yl acetate; 4α,14‐dimethyl‐5α‐cholest‐8‐ene‐3,7,11‐trione; 4α,14‐dimethyl‐5α‐cholesta‐7,9(11)‐dien‐3‐one and 4α,14‐dimethyl‐5α‐cholest‐8‐en‐3β‐yl acetate), previously prepared from 31‐norlanostenol, a natural insecticide isolated from the latex of Euphorbia officinarum, have been subjected to oxidation with hydrogen peroxide (H2O2) and iodosobenzene (PhIO) catalyzed by porphyrin complexes (cytochrome P‐450 models) in order to obtain optimized derivatives with high regioselectivity. The main transformations were epoxidation of the double bonds and hydroxylations of non‐activated C–H groups and the reaction products were 25‐hydroxy‐4α,14‐dimethyl‐5α‐cholesta‐7,9(11)‐dien‐3β‐yl acetate (59 %), 25‐hydroxy‐4α,14‐dimethyl‐5α‐cholest‐8‐ene‐3,7,11‐trione (60 %), 4α,14‐dimethyl‐5α,7β‐7,8‐epoxycholest‐9(11)‐en‐3‐one (22 %), 8‐hydroxy‐4α,14‐dimethyl‐5α‐cholest‐9(11)‐ene‐3,7‐dione (16 %), 12α‐hydroxy‐4α,14‐dimethyl‐5α,7β‐7,8‐epoxycholest‐9(11)‐en‐3‐one (16 %), and 4α,14‐dimethyl‐5α,8α‐8,9‐epoxycholestan‐3β‐yl acetate (26 %), respectively. We also investigated the insect (Myzus persicae, Rhopalosiphum padi and Spodoptera littoralis) antifeedant and postingestive effects of these terpenoid derivatives. None of the compounds tested had significant antifeedant effects, however, all were more effective postingestive toxicants on S. littoralis larvae than the natural compound 31‐norlanostenol, with 4α,14‐dimethyl‐5α,8α‐8,9‐epoxycholestan‐3β‐yl acetate being the most active. The study of their structure–activity relationships points out at the importance of C3 and C7 substituents.

Scavengome of an Antioxidant

“…This is based on biocompatibility or translational goodness in terms of bioequivalence, i.e., oxidative transformation of an antioxidant by any chemical system can be classified as a biorelevant (A), biomimetic (B), or biomimetic-related chemical (C) oxidation. Accordingly, we consider biorelevant (A) any in vitro chemical models that directly provide oxidative agents/free radicals present in the body, such as • OH: metalloporphyrin/H2O2 (Mazoir et al, 2020), Fe 2+ /H2O2 (Miller et al, 2021), H2O2: Cu 2+ /ascorbic acid ( Shen et al, 2021), andONOO -(Ferrer-Sueta et al, 2018), and chemical systems for which there is significant experimental evidence of their suitability for biological oxidative stress (DPPH, AAPH, AIBN AMVN) (Marano et al, 2021;Takatsuka et al, 2022) are also included in this group. We classify as biomimetic (B) the chemical systems in which the oxidative reaction medium contains an aqueous component in addition to a cosolvent (in some cases dissolved O2 as a prooxidant) providing a medium with better suitability to the physiological system.…”

Biological Properties of Latex, Aqueous Extracts and Bee Products of Euphorbia officinarum L.: A Short Review

“…Epoxidation of the double bonds and hydroxylations of non-activated C–H groups of semisynthetic functionalized triterpenes 4α,14-dimethyl-5α,8α-8,9-epoxy-chole-stan-3β-yl acetate ( 56 ); 4α,14-dimethyl-5α-cholest-8-ene-3,7,11-trione ( 32 ); 4α,14-dimethyl-5α-cholesta-7,9-dien-3-one ( 57 ) and 4α,14-dimethyl-5α-cholest-8-en-3β-yl acetate ( 58 ), previously prepared from 4α,14α-dimethyl-5α-cholest-8-en-3β-ol (a natural insecticide present in E. officinarum latex) were performed by Mazoir et al [ 57 ] with the purpose of obtaining optimized derivatives with high region selectivity and insecticidal activity. Several approaches had already been followed by this team and aforementioned.…”

“…Several approaches had already been followed by this team and aforementioned. In the work presented in 2020, Mazoir et al [ 57 ] used as reagents hydrogen peroxide (H 2 O 2 ) and iodosobenzene (PhIO) catalyzed by porphyrin complexes (cytochrome P-450 models). Under these conditions, the compounds obtained were: 25-hydroxy-4α,14-dimethyl-5α-cholest-7,9-dien-3β-yl acetate ( 59 ), 25-hydroxy-4α,14-dimethyl-5α-cholest-8-ene3,7,11-trione ( 60 ), 4α,14-dimethyl-5α,7β-7,8-epoxychol-est-9-en-3-one ( 61 ), 8-hydroxy-4α,14-dimethyl-5α-cholest-9-ene-3,7-dione ( 62 ), 12α-hydroxy-4α,14-dimethyl-5α,7β-7,8-epoxycholest-9-en-3-one ( 63 ), and 4α,14-dimethyl-5α,8α-8,9-epoxycholestan-3β-yl acetate ( 64 ).…”

“…Under these conditions, the compounds obtained were: 25-hydroxy-4α,14-dimethyl-5α-cholest-7,9-dien-3β-yl acetate ( 59 ), 25-hydroxy-4α,14-dimethyl-5α-cholest-8-ene3,7,11-trione ( 60 ), 4α,14-dimethyl-5α,7β-7,8-epoxychol-est-9-en-3-one ( 61 ), 8-hydroxy-4α,14-dimethyl-5α-cholest-9-ene-3,7-dione ( 62 ), 12α-hydroxy-4α,14-dimethyl-5α,7β-7,8-epoxycholest-9-en-3-one ( 63 ), and 4α,14-dimethyl-5α,8α-8,9-epoxycholestan-3β-yl acetate ( 64 ). The antifeedant and post-ingestive effects of these terpenoid derivatives were investigated for the insects M. persicae , R. padi and S. littoralis and Mazoir et al [ 57 ] concluded that none of the compounds tested had significant antifeedant effects. All were more effective post-ingestive toxicants on S. littoralis larvae than the natural 4α,14α-dimethyl-5α-cholest-8-en-3β-ol ( 9 ), with 4α,14-dimethyl-5α,8α-8,9-epoxychole-stan-3β-yl acetate ( 64 ) being the most active.…”

Chemical reactivities and molecular docking studies of parthenolide with the main protease of HEP-G2 and SARS-CoV-2

“…The formed epoxides [2] , [3] , [4] , [5] , [6] represent an extremely useful intermediate which could be converted to higher value chemical compounds [7] . Moreover, epoxides are present in a large range of natural products [ 8 , 9 ] and biologically active compounds [10] , [11] , [12] , [13] . Epoxides can be accessed in numerous ways, but the most common method consist the epoxidation of olefins using peracids [14] .…”