Gram-scale approach for ß-costic acid via allylic oxidation of ß-selinene.

ß-Costic acid is a sesquiterpene phytoalexin with acaricidal activity against Varroa destructor and antitrypanosomal activity. A concise and efficient method was developed for the synthesis of ß-costic acid via the allylic oxidation of ß-selinene, a component of celery seed oil.

Structural modification of (3E)-4,8-dimethyl-1,3,7-nontriene enhances its ability to kill Plutella xylostella insect pests.

BACKGROUND: Plant secondary metabolites and their modified derivatives play an important role in the discovery and development of novel insecticides. The natural plant product (3E)-4,8-dimethyl-1,3,7-nontriene (DMNT) has been proven to be able to effectively repel and kill the lepidopteran insect pest Plutella xylostella. RESULTS: In this study, four oxygenated derivatives of DMNT were synthesized by allylic hydroxylation and subsequent etherification or esterification. Bioassays on P. xylostella larvae showed that the compounds DMNT-OCH3 (2), DMNT-OCy (3) and DMNT-OAc (4) were more toxic to the larvae than DMNT alone. The most pronounced effect was observed for compound 2, which showed a 22.23% increase in lethality at a concentration of 0.25 µm. Moreover, the peritrophic matrix (PM) barrier in the insect midgut was more severely damaged by compounds 2, 3 and 4 than by DMNT. The median lethal concentration (LC50 , 48 h) of compounds 2, 3 and 4 on P. xylostella was determined to be 0.98, 1.13 and 1.11 mg mL-1 , respectively, which is much lower than the commercial insecticides eucalyptol (2.89 mg mL-1 ) and thymol (2.45 mg mL-1 ). CONCLUSION: These results suggested that oxygenated DMNT derivatives offer a significantly improved killing effect over DMNT on P. xylostella. This work has provided a basis for further design, structural modification and development of DMNT as botanical insecticides. © 2023 Society of Chemical Industry.

Synthesis of 1,3-Dioxan-2-ones by Photo-Aerobic Selenium-π-Acid Multicatalysis.

An expedient method for the synthesis of cyclic carbonates from homoallylic carbonic acid esters by means of photo-aerobic selenium-π-acid multicatalysis is reported. Until now, conceptually related methods commonly relied either on the stoichiometric addition of electrophiles onto the substrate's alkene moiety or the presence of pre-installed leaving groups in allylic position of said alkene to - in part, catalytically - initiate an intramolecular attack by an adjacent carbonic acid ester group. In sharp contrast, the current study shows that the C-C double bond of homoallylic carbonic acid esters can be directly activated by the catalytic interplay of a pyrylium dye and a diselane using ambient air as the sole oxidant and visible light as an energy source.

Enzyme-catalyzed allylic oxidation reactions: A mini-review.

Chiral allylic oxidized products play an increasingly important role in the pharmaceutical, agrochemical, and pharmaceutical industries. Biocatalytic C-H oxyfunctionalization to synthesize allylic oxidized products has attracted great attention in recent years, with the ability to simplify synthetic approaches toward complex compounds. As a result, scientists have found some new enzymes and mutants through techniques of gene mining and enzyme-directed evolution in recent years. This review summarizes the recent developments in biocatalytic selective oxidation of olefins by different kinds of biocatalysts.

Non-Palladium-Catalyzed Approach to the Synthesis of (E)-3-(1,3-Diarylallylidene)Oxindoles.

Two novel synthetic approaches for synthesizing (E)-3-(1,3-diarylallylidene)oxindoles from oxindole were developed. All previously reported methods for synthesizing 3-(1,3-diarylallylidene)oxindoles utilized palladium-catalyzed reactions as a key step to form this unique skeleton. Despite high efficiency, palladium-catalyzed reactions have limitations in terms of substrate scope. Especially, an iodoaryl moiety cannot be introduced by the previous methods due to its high reactivity toward the palladium catalyst. Our Knoevenagel/allylic oxidation/Wittig and Knoevenagel/aldol/dehydration strategies complement each other and show broad substrate scope, including substrates with iodoaryl groups. The current methods utilized acetophenones, benzylidene phosphonium ylides, and benzaldehydes that are commercially available or easily accessible. Thus, the current synthetic approaches to (E)-3-(1,3-diarylallyldiene)oxindoles are readily amendable for variety of oxindole derivatives.

Iron and manganese lipoxygenases of plant pathogenic fungi and their role in biosynthesis of jasmonates.

Lipoxygenases (LOX) contain catalytic iron (FeLOX), but fungi also produce LOX with catalytic manganese (MnLOX). In this review, the 3D structures and properties of fungal LOX are compared and contrasted along with their associations with pathogenicity. The 3D structures and properties of two MnLOX (Magnaporthe oryzae, Geaumannomyces graminis) and the catalysis of four additional MnLOX have provided information on the metal centre, substrate binding, oxygenation, tentative O2 channels, and biosynthesis of exclusive hydroperoxides. In addition, the genomes of other plant pathogens also code for putative MnLOX. Crystals of the 13S-FeLOX of Fusarium graminearum revealed an unusual altered geometry of the Fe ligands between mono- and dimeric structures, influenced by a wrapping sequence extension near the C-terminal of the dimers. In plants, the enzymes involved in jasmonate synthesis are well documented whereas the fungal pathway is yet to be fully elucidated. Conversion of deuterium-labelled 18:3n-3, 18:2n-6, and their 13S-hydroperoxides to jasmonates established 13S-FeLOX of F. oxysporum in the biosynthesis, while subsequent enzymes lacked sequence homologues in plants. The Rice-blast (M. oryzae) and the Take-all (G. graminis) fungi secrete MnLOX to support infection, invasive hyphal growth, and cell membrane oxidation, contributing to their devastating impact on world production of rice and wheat.

A New Dimeric Copper(II) Complex of Hexyl Bis(pyrazolyl)acetate Ligand as an Efficient Catalyst for Allylic Oxidations.

A new dimeric copper(II) bromide complex, [Cu(LOHex)Br(µ-Br)]2 (1), was prepared by a reaction of CuBr2 with the hexyl bis(pyrazol-1-yl)acetate ligand (LOHex) in acetonitrile solution and fully characterized in the solid state and in solution. The crystal structure of 1 was also determined: the complex is interlinked by two bridging bromide ligands and possesses terminal bromide ligands on each copper atom. The two pyrazolyl ligands in 1 coordinate with the nitrogen atoms to complete the Cu coordination sphere, resulting in a five-coordinated geometry-away from idealized trigonal bipyramidal and square pyramidal geometries-which can better be described as distorted square pyramidal, as measured by the τ and χ structural parameters. The pendant hexyloxy chain is disordered over two arrangements, with final site occupancies refined to 0.705 and 0.295. The newly synthesized complex was evaluated as a catalyst in copper-catalyzed C-H oxidation for allylic functionalization through a Kharasch-Sosnovsky reaction without any external reducing agent. Using 0.5 mol% of this catalyst, and tert-butyl peroxybenzoate (Luperox) as an oxidant, allylic benzoates were obtained with up to 90% yield. The general reaction time was only slightly decreased to 24 h but a very significant decrease in the alkene:Luperox ratio to 3:1 was achieved. These factors show relevant improvements with respect to classical Kharasch-Sosnovsky reactions in terms of rate and amount of reagents. The present study highlights the potential of copper(II) complexes containing functionalized bis(pyrazol-1-yl)acetate ligands as efficient catalysts for allylic oxidations.

The allylic oxidation of tigliane esters.

As part of a study on the structure-activity relationships of the anticancer agent tigilanol tiglate (EBC-46, 2), the allylic oxidation of phorbol triacetate (1c) and of the acetonide of its 3αH-dihydroderivative (5) was investigated. The aim was to introduce an oxygen function at C-5 en route to point-like analogues of 2, but functionalization of C-10 was instead observed. This was followed by oxidative fragmentation of ring B to the 9,10-secotigliane derivative 6 and oxidation of the endocyclic Δ6 double bond to the C-6/C-10 oxygen bridged 7-oxotigliane 7. Despite the over-functionalization of ring B, these observations suggest the possibility to modify positions overlooked in the oxidase phase of tigliane biosynthesis and explore novel areas of the phorbol chemical space.

Modulation of the Activity of Gold Clusters Immobilized on Functionalized Mesoporous Materials in the Oxidation of Cyclohexene via the Functional Group. The Case of Aminopropyl Moiety.

Gold nanoclusters and isolated gold atoms have been produced in a two-liquid phase procedure that involves a solution of gold in aqua regia and rosemary essential oil as organic layer. These gold entities have been immobilized on the ordered mesoporous silica material SBA-15 functionalized with different amounts of aminopropyl groups. The resulting materials have been characterized by XRD, N2 adsorption, chemical analysis, TGA, 29Si MAS NMR, 13C CP/MAS NMR, UV-vis spectroscopy, XPS, and STEM. The Au-containing materials retain the ordering and porosity of the pristine support. Gold content varies in the range of 0.07-0.7 wt% as a function of the specific immobilization conditions, while STEM evidences the presence of isolated gold atoms. XPS shows a shift of the Au 4f BE toward values lower than those of metallic gold. The catalytic activity in the oxidation of cyclohexene with molecular oxygen at atmospheric pressure parallels the Au content of the aminopropyl-SBA-15 supports. This activity is higher than that of analogous Au entities immobilized on SBA-15 functionalized with thiol or sulfonate groups, the activity decreasing in the order Au-NH2 > Au-SO3- > Au-SH. This behavior has been attributed to differences in the interaction strength between the functional group and the Au entities, which is optimum for the aminopropyl groups.

Biocatalytic allylic hydroxylation of unsaturated triterpenes and steroids by Bacillus megaterium CGMCC 1.1741.

In this study, we described the microbial catalyzed allylic oxidation by Bacillus megaterium CGMCC 1.1741 of three Δ12-pentacyclic triterpenes, erythrodiol (1), uvaol (2), hederagenin (3) and of four steroids including Δ5-steroids, diosgenin (4), pennogenin (5), 25(R,S)-ruscogenin (6) and Δ4-steroid, diosgenone (7). As a result, fourteen metabolites were generated with allyl hydroxyl moiety. Ten (1a-c, 2a, 2c, 3a, 5a-b, and 6a-b) of them were new natural products and their structures were determined on the basis of 1D/2D NMR and HR-MS data. Biocatalytic allylic oxidation by B. megaterium CGMCC 1.1741 is thus a potential non-toxic and efficient alternative method toward metal-mediated oxidation procedures in the synthesis of natural products and medicines.

Scalable Preparation of Enantioenriched (S)-5-methylhept-2-en-4-one. Synthesis and Aroma Properties of Achiral Analogues Thereof.

(S)-5-Methylhept-2-en-4-one is a key flavour compound in hazelnuts. We have performed its chiral-pool-based chemoenzymatic synthesis with 39% overall yield (73% ee). The four-step aldol-based sequence avoids the use of highly reactive and/or toxic reagents, does not require anhydrous conditions and uses only distillation as the purification method. Thus, such methodology represents a green and scalable alternative to only two stereoselective approaches towards this natural product known so far. In addition, we have designed and prepared a set of new (di)enones as achiral synthetic analogues of the title compound. The results of their sensory analyses clearly show that relatively minor structural changes of the natural molecule significantly alter its olfactory properties. Thus, simple (poly)methylation completely changes the original hazelnut aroma of (S)-5-methylhept-2-en-4-one and shifts the odour of its analogues to eucalyptus, menthol, camphor, and sweet aroma.

Metal-Free Allylic Oxidation of Steroids Using TBAI/TBHP Organocatalytic Protocol.

A mild, efficient and organocatalytic allylic oxidation of steroids using a TBAI/TBHP protocol has been developed. A range of bioactive Δ5 -en-7-ones can be easily prepared from the corresponding Δ5 -steroids. The methodology features several advantages, including readily available starting materials, environmentally benign oxidant, high functional group compatibility, and metal-free catalysis.

Cell-free one-pot conversion of (+)-valencene to (+)-nootkatone by a unique dye-decolorizing peroxidase combined with a laccase from Funalia trogii.

A combined system of a unique dye-decolorizing peroxidase (Ftr-DyP) and a laccase obtained from the basidiomycete Funalia trogii converted the precursor (+)-valencene completely to the high-value grapefruit flavour constituent (+)-nootkatone, reaching a concentration maximum of 1100 mg/L. In the presence of 1 mM Mn2+ and 2.5 mM p-coumaric acid, (+)-nootkatone was the predominating volatile product, and only traces of substrate and the nootkatols were detectable after 24 h. Hence, the two-enzyme-system reproduced the oxidizing activity observed before for the crude culture supernatant. The newly discovered Ftr-DyP was purified, sequenced and further characterized as a thermostable, non-glycosylated protein with a pH-optimum in the acidic range and a calculated mass of 52.3 kDa. Besides the typical activity of DyPs towards anthraquinone dyes, Ftr-DyP also oxidized Mn2+ and showed activity in the absence of hydrogen peroxide. Neither the DyP from Mycetinis scorodonius nor the manganese peroxidase from Nematoloma frowardii were able to replace Ftr-DyP in this reaction. A hypothetical reaction mechanism is presented.

Synthesis and characterization of cobalt-supported catalysts on modified magnetic nanoparticle: Green and highly efficient heterogeneous nanocatalyst for selective oxidation of ethylbenzene, cyclohexene and oximes with molecular oxygen.

In this study, a new supported cobalt nanocatalyst has been described. The Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) modified by SiO2/aminopropyl trimethoxy silane/cyanuric chloride (Fe3O4@SiO2-APTMS/CC) utilized for anchoring metformin-cobalt complex (Fe3O4 Ms@SiO2-APTMS/CC/Met@Co(II)). The structure of novel complex well defined by elemental analysis, ICP, AAS, BET, FT-IR, EDX, SEM, TEM, DLS, XRD, TG-DTG, VSM and XPS. The catalytic efficiency of the synthesized cobalt nanocatalyst was studied in the oxidation of ethylbenzene (EB), cyclohexene (CYHE) and various oximes using molecular oxygen as ecofriendly oxidant and high catalytic activity and selectivity toward oxidation is observed. Selective aerobic oxidation of EB and CYHE and various oximes catalyzed by the cobalt nanocatalyst without any reducing agent by using N-hydroxyphthalimide (NHPI), gave acetophenone (AcPO), 2-cyclohexene-1-one and corresponding carbonyl compounds respectively, as major products. To achieve high level of efficiency of heterogeneous nanocatalyst, various parameters such as the ratio and amount of nanocatalyst/NHPI, reaction time, temperature and solvents were evaluated. The easily preparation from inexpensive and commercially available reagent, thermal stability, suitable performance in reusability, high efficiency and selectivity in oxidation reactions, short reaction time, easy recovery and separation from reaction mixture, are advantages of this novel catalyst.

Bioproduction of α-humulene in metabolically engineered Escherichia coli and application in zerumbone synthesis.

Zerumbone is a sesquiterpene ketone with potent anti-cancerogenic activities, produced in several ginger species of the Zingiberaceae familiy. We have investigated the biotechnological production of α-humulene, a precursor of zerumbone. By implementing a heterologous mevalonate pathway in combination with the α-humulene synthase expression, we effectively synthesized α-humulene from glucose in Escherichia coli. In this study, we developed a practical and efficient in situ separation method for α-humulene by comparison of extractive and adsorptive strategies. By the in situ adsorption of the product to the hydrophobic resin Amberlite® XAD4 we were able to increase α-humulene yield by 2310% to 60.2 mg/L. Furthermore we present an easy applicable, short subsequent chemical process for the conversion of α-humulene to zerumbone by using transition metal catalysis. To reduce process steps, the chemical reaction was carried out in the same solvent as the eluting solvent that was used to elute α-humulene from the adsorbent resin. By allylic oxidation of α-humulene with manganeseII chloride as a catalyst and tert.-butylhydroperoxide as an oxidizing agent we were able to synthetize zerumbone with a selectivity of 51.6%. Product and byproducts of the oxidation reaction were identified by GC-MS.

Oxidation of Hindered Allylic C-H Bonds with Applications to the Functionalization of Complex Molecules.

We report the palladium-catalyzed oxidation of hindered alkenes to form linear allylic esters. The combination of palladium(II) benzoate, 4,5-diazafluoren-9-one, and benzoquinone catalyzes the mild oxidation of terminal alkenes with tert-butyl benzoyl peroxide as an oxidant in the presence of diverse functional groups. Selective oxidation of terminal alkenes in the presence of trisubstituted and disubstituted alkenes has been achieved, and the ability to conduct the reaction on a gram scale has been demonstrated. The mild conditions and high tolerance for auxiliary functionality make this method suitable for the synthesis and derivatization of complex molecules.

Catalytic Asymmetric Intermolecular Allylic Functionalization of Unactivated Internal Alkenes.

The asymmetric allylic functionalization of unactivated internal alkenes is an emerging strategy for the conversion of simple unsaturated starting materials into a diverse range of enantioenriched products. This Perspective summarizes the development of reactions wherein a chiral catalyst facilitates the intermolecular stereoselective reaction between an achiral unactivated internal alkene and a reagent.

Electrochemical Allylic Oxidation of Olefins: Sustainable and Safe.

The power you're supplying: With the application of an optimized electrochemical approach, the allylic oxidation of olefins, which is an important C-H activation process that provides access to enones, becomes a sustainable, versatile, and potent key reaction for organic synthesis.

Electrochemical oxidation of cholesterol.

Indirect cholesterol electrochemical oxidation in the presence of various mediators leads to electrophilic addition to the double bond, oxidation at the allylic position, oxidation of the hydroxy group, or functionalization of the side chain. Recent studies have proven that direct electrochemical oxidation of cholesterol is also possible and affords different products depending on the reaction conditions.

N-Hydroxyphthalimide catalyzed allylic oxidation of steroids with t-butyl hydroperoxide.

A new and optimized procedure for the allylic oxidation of Δ(5)-steroids with t-butyl hydroperoxide in the presence of catalytic amounts of N-hydroxyphthalimide (NHPI) under mild conditions was developed, showing excellent regioselectivity and chemoselectivity (functional group compatibility). It was found that Co(OAc)2 could enhance the catalytic ability of NHPI resulting in better yields and shorter reaction times. The reaction mechanism and the scope of the reaction with a variety of Δ(5)-steroidal substrates were also investigated.