Silica Gel-mediated Oxidation of Prenyl Motifs Generates Natural Product-Like Artifacts

Prenyl moieties are commonly encountered in the natural products of terpenoid and mixed biosynthetic origin. The reactivity of unsaturated prenyl motifs is less recognized and shown here to affect the acyclic Rhodiola rosea monoterpene glycoside, kenposide A (8), which oxidizes readily on silica gel when exposed to air. The major degradation product mediated under these conditions was a new aldehyde, 9. Exhibiting a shortened carbon skeleton formed through the breakdown of the terminal isopropenyl group, 9 is prone to acetalization in protic solvents. Further investigation of minor degradation products of both 8 and 8-prenylapigenin (8-PA, 12), a flavonoid with an ortho-prenyl substituent, revealed that the aldehyde formation was likely realized through epoxidation and subsequent cleavage at the prenyl olefinic bond. Employment of 1H NMR full spin analysis (HiFSA) achieved the assignment of all chemical shifts and coupling constants of the investigated terpenoids and facilitated the structural validation of the degradation product, 9. This study indicates that prenylated compounds are generally susceptible to oxidative degradation, particularly in the presence of catalytic mediators, but also under physiological conditions. Such oxidative artifact/metabolite formation leads to a series of compounds with prenyl-derived (cyclic) partial structures that are analogous to species formed during Phase I metabolism in vivo. Phytochemical and pharmacological studies should take precautions or at least consider the impact of (unavoidable) exposure of prenyl-containing compounds to catalytic and/or oxidative conditions.

Quantum Chemical Investigation of the Formation of Spiroheterocyclic Compounds Via the (3 + 2) Cycloaddition Reaction of 1-methyl-3-(2,2,2-trifluoroethylidene)pyrrolidin-2-one with Diazomethane and Nitrone Derivatives

Spirocycles are important structures in drug development due to their inherent biological activity. Their complex architecture usually presents many synthetic difficulties which are efficiently resolved with detailed theoretical studies. The chemo-, regio- and stereoselectivities of the formation of spiroheterocyclic compounds via the (3 + 2) cycloaddition (32CA) reaction of 1-methyl-3-(2,2,2-trifluoroethylidene)pyrrolidin-2-one (A1) derivatives with diazomethane and nitrone derivative have been studied at the M06-2X/6-311G(d,p) level of theory. The reactions of diazomethane (A2) and N-methyl-C-phenyl nitrone (A3) derivatives with 1-methyl-3-(2,2,2-trifluoroethylidene)pyrrolidin-2-one derivatives (A1) occurs chemoselectively along the olefinic bond of A1 via an asynchronous one-step mechanism. Analysis of the electrophilic ( and nucleophilic ( Parr functions at the different reaction sites in A1 shows that A2 and A3 add across the atomic centers with the largest Mulliken and NBO atomic spin densities. Both electron-donating groups (EDGs) and electron-withdrawing groups (EWGs) on the A3 molecule do not affect the observed preferred pathway in its 32CA reaction with A1 whereas the electronic and steric nature of the substituent on the A2 molecule influences the preferred pathway in the 32CA reaction of A1 and A2. The title reaction proceeds via forward electron denisity flux (FEDF), where electron density fluxes from the three-atom components (A2 and A3) to A1. The computed global electron density transfer (GEDT) values suggest that the 32CA of A1 with diazomethane is a polar reaction while the 32CA reaction of A1 with N-methyl-C-phenyl nitrone is a non-polar reaction, and an inverse relationship has been established between the polar character of the reactions and activation barriers. In all the reactions studied, the selectivities are kinetically controlled.

Kinetics of CH2=CHCH2OCF2CF2H with atmospheric oxidants

<p>As industries transition towards greener business models, many mass-produced chemicals are being replaced by low-global warming potential (GWP) alternatives. Allyl 1,1,2,2-tetrafluoroethyl ether (CH<sub>2</sub>=CHCH<sub>2</sub>OCF<sub>2</sub>CF<sub>2</sub>H) represents a potential replacement candidate. This molecule contains an olefinic bond, several abstractable hydrogen atoms, an ether linkage and a non-perfluorinated side-chain. As such it can react with various atmospheric oxidants in a variety of degradation mechanisms, each of which may serve to reduce its atmospheric lifetime and its impact upon the environment. Before widespread usage, it is crucial that these environmental sinks are quantified such that the risk that CH<sub>2</sub>=CHCH<sub>2</sub>OCF<sub>2</sub>CF<sub>2</sub>H poses to the environment can be thoroughly assessed. We present measurements of gas-phase relative rates with hydroxyl radicals (OH), atomic chlorine (Cl), ozone (O<sub>3</sub>) and nitrate radical (NO<sub>3</sub>) carried out in HELIOS simulation chamber at CNRS (Orléans, France) as described by Ren <em>et al</em>.<sup>1</sup> and references within. Although previous measurements are available for OH<sup>2</sup> and Cl,<sup>3</sup> we find some discrepancies in comparison to our new determinations. In the case of O<sub>3</sub> and NO<sub>3</sub>, these represent the first such measurements of which we are aware. Furthermore, we have determined the absolute rate coefficient of CH<sub>2</sub>=CHCH<sub>2</sub>OCF<sub>2</sub>CF<sub>2</sub>H + OH using a pulsed-laser photolysis–laser-induced fluorescence technique between 273 and 363 K performed at the Physical Chemistry department of UCLM (Ciudad Real, Spain) as described by Blázquez <em>et al</em>.<sup>4</sup> and references within, representing the first temperature-dependent kinetic measurements for this molecule with OH radicals. In addition, the infrared absorption cross section is quantified between 400 and 4000 cm<sup>-1</sup>, in an extended range of wavenumbers with respect to the previously reported ones<sup>5</sup>. Combining each these observations, we are able to provide an improved estimate for the GWP of this molecule and its likely environmental fate.</p><p> </p><p>References:</p><p><span>1. Ren, Y.; McGillen, M. R.; Daële, V.; Casas, J.; Mellouki, A. Science Total Environ. </span><strong>2020</strong><span>, 749, 141406.</span></p><p>2. Heathfield, A. E.; Anastasi, C.; Pagsberg, P.; McCulloch, A. Atmos. Environ. <strong>1998,</strong> 32, 711–717.</p><p>3. Papadimitriou, V. C.; Kambanis, K. G.; Lazarou, Y. G.; Papagiannakopoulos, P. J. Phys. Chem. A <strong>2004,</strong> 108, 2666–2674.</p><p>4. Blázquez, S.; Antiñolo, M.; Nielsen, O. J.; Albaladejo, J.; Jiménez, E. Chem. Phys. Lett. <strong>2017</strong>, 687, 297–302.</p><p>5. Heathfield, A. E.; Anastasi, C.; McCulloch, A.; Nicolaisen, F. M. Atmos. Environ. <strong>1998</strong>, 32, 2825–2833.</p>

Elucidating the differences in oxidation of high-performance α- and β- diisobutylene biofuels via Synchrotron photoionization mass spectrometry

Biofuels are a promising ecologically viable and renewable alternative to petroleum fuels, with the potential to reduce net greenhouse gas emissions. However, biomass sourced fuels are often produced as blends of hydrocarbons and their oxygenates. Such blending complicates the implementation of these fuels in combustion applications. Variations in a biofuel’s composition will dictate combustion properties such as auto ignition temperature, reaction delay time, and reaction pathways. A handful of novel drop-in replacement biofuels for conventional transportation fuels have recently been down selected from a list of over 10,000 potential candidates as part of the U.S. Department of Energy’s (DOE) Co-Optimization of Fuels and Engines (Co-Optima) initiative. Diisobutylene (DIB) is one such high-performing hydrocarbon which can readily be produced from the dehydration and dimerization of isobutanol, produced from the fermentation of biomass-derived sugars. The two most common isomers realized, from this process, are 2,4,4-trimethyl-1-pentene (α-DIB) and 2,4,4-trimethyl-2-pentene (β-DIB). Due to a difference in olefinic bond location, the α- and β- isomer exhibit dramatically different ignition temperatures at constant pressure and equivalence ratio. This may be attributed to different fragmentation pathways enabled by allylic versus vinylic carbons. For optimal implementation of these biofuel candidates, explicit identification of the intermediates formed during the combustion of each of the isomers is needed. To investigate the combustion pathways of these molecules, tunable vacuum ultraviolet (VUV) light (in the range 8.1–11.0 eV) available at the Lawrence Berkeley National Laboratory’s Advanced Light Source (ALS) has been used in conjunction with a jet stirred reactor (JSR) and time-of-flight mass spectrometry to probe intermediates formed. Relative intensity curves for intermediate mass fragments produced during this process were obtained. Several important unique intermediates were identified at the lowest observable combustion temperature with static pressure of 93,325 Pa and for 1.5 s residence time. As this relatively short residence time is just after ignition, this study is targeted at the fuels’ ignition events. Ignition characteristics for both isomers were found to be strongly dependent on the kinetics of C4 and C7 fragment production and decomposition, with the tert-butyl radical as a key intermediate species. However, the ignition of α-DIB exhibited larger concentrations of C4 compounds over C7, while the reverse was true for β-DIB. These identified species will allow for enhanced engineering modeling of fuel blending and engine design.

Natural Products Containing Olefinic Bond: Important Substrates for Semi-synthetic Modification Towards Value Addition

: Semi-synthesis, the way of preparing novel bioactive molecules via modification of compounds isolated from natural sources is very much useful nowadays in the drug discovery process. The modification is based on the reaction of functional group(s) present in a natural compound. Among the examples of functional group transformation, double bond modification is also common in the literature. Several reactions like hydrogenation, cyclopropanation, epoxidation, addition reaction (halogenations, hydroxylation), Michael addition, Heck reaction, cycloaddition, dipolar cycloaddition, etc. are employed for this purpose. In this review, we have tried to gather the reactions performed with several double bond containing classes of natural products like diterpenes, xanthones, sesquiterpene exomethylene lactones, diaryl heptanoids, steroidal lactones, triterpenoids, limonoids, and alkamides. Where available, the effects of transformations on the biological activities of the molecules are also mentioned.

DFT Mechanistic Study on the Reaction of Benzenesulfonyl Azides with Oxabicyclic Alkenes

The reaction of benzenesulfonyl azides with oxabicyclic alkenes to form aziridines, reported by Chen et al (J. Org. Chem. 2019, 84, 18, 11863-11872), could proceed via initial [3+2] cycloaddition to form triazoline intermediates followed by dinitrogen cleavage or via initial dinitrogen cleavage of the benzenesulfonyl azide to afford a nitrene intermediate followed by insertion of this species into the olefinic bond of the oxabicyclic alkene. Calculations at the DFT M06-2X/6-311G+(d,p) level show that the initial [3+2] cycloaddition has barriers of 17.3 kcal/mol (endo) and 10.2 kcal/mol (exo) while the initial nitrogen extrusion step has a barrier of 38.9 kcal/mol. The rate-determining step along the former pathway is the dinitrogen cleavage from triazoline cycloadducts which has barriers of 32.3 kcal/mol (endo) and 38.6 kcal/mol (exo) and that along the latter pathway is dinitrogen cleavage from benzenesulfonyl azide with an activation of barrier of 38.9 kcal/mol. The [3+2] addition of benzenesulfonyl azide with oxabicyclic alkene to afford endo and exo triazoline intermediates is kinetically favored over the dinitrogen cleavage from benzenesulfonyl azide by 21.6 and 28.1 kcal/mol for endo and exo pathway respectively. Thus, the preferred pathway for the reaction of oxabicyclic alkene with benzenesulfonyl azide is via initial [3+2] addition followed by dinitrogen cleavage, contrary to the proposal by Chen et al. The lower activation barrier for the dinitrogen extrusion step leading to endo aziridine compared to exo isomer means that the endo product will be formed as the major product, confirming the experimental observation. The position of substituents on the benzene group of the benzenesulfonyl azide greatly affects the endo / exo diastereoselectivity.

Catalytic Oxidation Processes for the Upgrading of Terpenes: State-of-the-Art and Future Trends

Terpenic olefins constitute a relevant platform of renewable molecules, which could be used as key intermediates for the perfumery, flavoring, and pharmaceutical industries. The upgrading of these cheap and available agro-resources through catalytic oxidation processes remains of great interest, leading to the formation of either epoxides via the oxidation of the olefinic bond or α,β-unsaturated ketones by the Csp3-H functionalization at the α-position of the double bond. This critical review summarizes some of the most relevant homogeneous or heterogeneous catalysts designed for the oxidation of some abundant terpenic olefins in the last decade (2008–2018).

A Concise and Stereoselective Total Synthesis of Pestalotioprolide C Using Ring-Closing Metathesis

The stereoselective total synthesis of the pestalotioprolide C is disclosed in 13 linear steps in 4% overall yield. The key steps in this approach are a ring-closing-metathesis protocol for the construction of the 14-membered macrolide with E-olefinic bond, a Keck allylation, and a Sharpless kinetic resolution for the installation of desired stereocenters at C4 and C7.