C3 Double Bond Research Articles

Flow chemistry-enabled asymmetric synthesis of cyproterone acetate in a chemo-biocatalytic approach

Flow chemistry has many advantages over batch synthesis of organic small-molecules in terms of environmental compatibility, safety and synthetic efficiency when scale-up is considered. Herein, we report the 10-step chemo-biocatalytic continuous flow asymmetric synthesis of cyproterone acetate (4) in which 10 transformations are combined into a telescoped flow linear sequence from commercially available 4-androstene-3, 17-dione (11). This integrated one-flow synthesis features an engineered 3-ketosteroid-Δ1-dehydrogenase (ReM2)-catalyzed Δ1-dehydrogenation to form the C1, C2-double bond of A ring, a substrate-controlled Co-catalyzed Mukaiyama hydration of 9 to forge the crucial chiral C17α-OH group of D ring with excellent stereoselectivity, and a rapid flow Corey-Chaykovsky cyclopropanation of 7 to build the cyclopropyl core of A ring. By strategic use of these three key reactions and fully continuous-flow operations, cyproterone acetate (4) is produced in an overall yield of 9.6% in 3 h of total reaction time, this is the highest total number of chemical transformation performance in any other continuous-flow synthesis reported to date.

Flavonoids as Potential Modulators of Pancreatic Lipase Catalytic Activity

Background/Objectives: Obesity has reached pandemic proportions, with predictions suggesting that, by 2030, over 1.5 billion people will be affected. Pancreatic lipase (PL), the enzyme primarily responsible for the absorption of dietary lipids, presents a potential target for obesity management. However, while porcine pancreatic lipase (PPL) is commonly used as the enzyme source for screening potential inhibitors, its effect on human pancreatic lipase (HPL) is rarely reported. This work aimed to screen the inhibitory effects of a library of flavonoids with different functional groups on the activity of PL from the human pancreas (triacylglycerol acyl hydrolase, EC 3.1.1.3) and compare it to the effects of the porcine pancreas (type II, EC 3.1.1.3), establishing, whenever possible, a structure–activity relationship. Methods: The inhibitory effects of a library of 48 flavonoids with different hydroxy, glycosyl, rutinosyl, galloyl, and extended alkyl groups were evaluated against PPL and HPL. The kinetic parameters and inhibitory mechanisms of the most active flavonoids were determined, and in silico docking studies of the more potent flavonoids were also performed, using the active site of HPL. Results/Conclusions: Variations in enzyme catalytic activity were observed depending on the source of the enzyme. The inhibitory effect was particularly influenced by the presence of extended alkyl groups at the C-3 of the C-ring and the C2=C3 double bond of the C-ring and the presence of a pyrogallol group at the C-2′, C-3′ and C-4′ of the B-ring. Docking results showed a strong correlation between docking scores and observed inhibitory activities, highlighting the critical role of specific substituents on the flavonoid backbone in enhancing detailed interaction dynamics with key amino acids. Compounds 28, 29, and 30, with alkyl groups, showed the highest docking scores, interacting with residues HIS151, PHE215, ARG256, and HIS263. Further analysis also revealed that specific substituents improved pocket occupancy and formed additional interactions with residues TYR114, PRO180, ILE209, and PHE215, which are crucial for inhibition. These binding characteristics closely mimic those observed with orlistat, reinforcing their mechanistic similarities in inhibiting HPL and validating their inhibitory activities.

Underlying Mechanisms of Chromatographic H/D, H/F, cis/trans and Isomerism Effects in GC-MS.

Charge-free gaseous molecules labeled with deuterium 2H (D) atoms elute earlier than their protium-analogs 1H (H) from most stationary GC phases. This effect is known as the chromatographic H/D isotope effect (hdIEC) and can be calculated by dividing the retention times (tR) of the protiated (tR(H) ) to those of the deuterated (tR(D)) analytes: hdIEC = tR(H)/tR(D). Analytes labeled with 13C, 15N or 18O have almost identical retention times and lack a chromatographic isotope effect. Derivatives of cis- and trans-analytes such as cis- and trans-fatty acids also differ in their retention times. Analytes that contain trans-C=C-double bonds elute earlier in gas chromatography-mass spectrometry (GC-MS) than their cis-C=C-double bonds containing congeners. The chromatographic cis/trans-effect (ctEC) can be calculated by dividing the retention times of the cis- by those of the trans-analytes: ctEC = tR(c)/tR(t). In the present work, the hdIEC and ctEC values of endogenous and exogenous substances were calculated from previously reported GC-MS analyses and found to range each between 1.0009 and 1.0400. The examination suggests that the H/D-isotope effects and the cis/trans-effects observed in GC-MS are based on differences in the inter-molecular interaction strengths of the analyte derivatives with the stationary phase of GC columns. The deuterium atoms, being larger than the H atoms of the analytes, attenuate the interaction of the skeleton of the molecules with the GC stationary phase. The angulation of trans-analytes decreases the interaction of the skeleton of the molecules with the GC stationary phase, as only parts of the molecules are close enough to the GC stationary phase to interact. Other chromatographic effects caused by hydrogen (H) and fluorine (F) atoms and by stereo-isomerism are considered to be based on a similar mechanism due to the different orientation of the side chains.

Biosynthesis of Bacteriochlorophylls and Bacteriochlorophyllides in Escherichia coli.

Photosynthesis, the most important biological process on Earth, converts light energy into chemical energy with essential pigments like chlorophylls and bacteriochlorophylls. The ability to reconstruct photosynthesis in heterotrophic organisms could significantly impact solar energy utilization and biomass production. In this study, we focused on constructing light-dependent biosynthesis pathways for bacteriochlorophyll (BChl) a and bacteriochlorophyllide (BChlide) d and c in the model strain Escherichia coli. The production of the starting compound, Mg protoporphyrin monomethylester, was optimized by screening the ribosome binding sites for the expression of each of the five genes. By fusing a maltose-binding protein and apolipoprotein A-I domain with the membrane protein BchF, the yield of 3-hydroxyethyl-Chlide a was increased by five-fold. Anaerobic cultivation of the engineered E. coli strains facilitated the reduction of the C7=C8 double bond by chlorophyllide a oxidoreductase, a critical step in BChl a synthesis. We further enhanced BChl a production by adjusting the isopropyl-β-d-thiogalactopyranoside concentration to optimize enzyme production and introducing an exogenous superoxide dismutase to combat oxidative stress. Additionally, fusing BciC with a RIAD tag resulted in an eight-fold increase in the production of 3-vinyl BChlide d. This study lays the foundation for the reconstitution of BChl-based photosynthetic apparatus in heterotrophic model organisms, offering promising avenues for future research and applications in biotechnology.

Nicht‐Kanonische C16 Homoterpen‐Biosynthese Weitverbreitet in Actinobakterien

AbstractEin neuartiger Biosyntheseweg zur seltenen und wenig Erforschten nicht‐kanonischen Familie der Homoterpene wurde in Actinobakterien durch gezieltes Genome‐Mining und enzymatische In vitro‐Rekonstitution entdeckt. Der Weg umfasst eine anfängliche methylierungsinduzierte Doppelbindungsisomerisierung von Farnesyldiphosphat (FPP) zu (2E,7E)‐6‐Methylfarnesyldiphosphat, katalysiert durch eine neuartige Familie von Methyltransferasen mit dualer Funktion. Das resultierende lineare C16‐Doppelbindungsisomer von FPP stellt das spezifische Substrat für eine neue Familie von Typ‐I‐Terpenzyklasen dar, die diverse Zyklisierungsreaktionen katalysieren. Funktionelle Charakterisierung von neun Enzympaaren führte zur Entdeckung von fünf bisher unbeschriebenen Homoterpen‐Naturstoffen. Die entdeckte Enzymologie ermöglicht die Entwicklung biokatalytischer und genetisch programmierbarer Systeme zur Herstellung methylierter Terpene mit potenziell neuartigen Eigenschaften („Magic‐Methyl‐Effekt“).

Non-Canonical C16 Homoterpene Biosynthesis Widespread in Actinobacteria.

A novel biosynthetic pathway towards the rare and underexplored non-canonical family of homoterpenes was discovered in actinobacteria through targeted genome mining and enzymatic in vitro reconstitution. The pathway comprises initial methylation-induced double bond isomerization of farnesyl diphosphate (FPP) to (2E,7E)-6-methyl-farnesyl diphosphate, catalyzed by a novel family of methyltransferases with unique dual function. The resulting linear C16 double bond isomer of FPP constitutes the specific substrate for a distinct family of type I terpene cyclases, catalyzing diverse cyclization reactions. Functional characterization of nine enzyme pairs led to discovery of five unprecedented homoterpene natural products. The enzymological novelty enables the development of novel biocatalytic and genetically programmable synthetic strategies towards methylated terpenoids with potentially unique properties ("magic methyl effect").

Engineering of Phycourobilin Synthase: PubS to a Two-Electron Reductase.

Phycourobilin:ferredoxin oxidoreductase (PubS) belongs to the ferredoxin-dependent bilin reductase (FDBR) family and catalyzes the reduction of the C15=C16 double bond, followed by the C4=C5 double bond of biliverdin IXα to produce phycourobilin. Among the diverse FDBR enzymes that catalyze site-specific reduction reactions of bilins, PubS lineage is the only one that reduces the C4=C5 double bond. This family can be broadly divided into four-electron reduction enzymes, which catalyze two successive two-electron reductions, such as PubS, and two-electron reduction enzymes, which catalyze a single two-electron reduction. The crystal structures of diverse FDBRs, excluding PubS, have unraveled that there are two distinct binding modes in the substrate-binding pocket. In this study, we focused on the arginine (Arg) residues that is considered crucial for substrate-binding mode in two-electron reduction enzymes. Through sequence alignment and comparison with the predicted structure of PubS, we identified a residue in PubS that corresponds to the Arg residue in the two-electron reduction enzymes. We further introduced mutations to avoid the steric hindrance associated with changes in the binding mode. Biochemical characterization of these variants showed that we successfully modified PubS from a four-electron reduction enzyme to a two-electron reduction enzyme with the accumulation of radicals. Our results provide insight into the molecular mechanisms of the chromophore binding mode and proton donation from acidic residues.

MEDT analysis of mechanism and selectivities in non-catalyzed and lewis acid-catalyzed diels–alder reactions between R-carvone and isoprene

Within the context of Molecular Electronic Density Theory (MEDT), this study investigates the Diels–Alder reaction among isoprene (2) and R-carvone (1R) applying DFT simulations, with and without Lewis acid (LA) catalysis. The results show that carvone (1R) acts as an electrophile and isoprene (2) as a nucleophile in a polar process. LA catalysis increases the electrophilicity of carvone, thereby improving the reactivity and selectivity of the reaction by reducing the activation Gibbs free energy. Parr functions reveal that the C5=C6 double bond is more reactive than the C9=C10 double bond, indicating chemoselectivity. The examination of the Electron Localization Function (ELF) reveals high regio- and stereoselectivity, indicating an asynchronous mechanism for the LA-catalyzed DA reaction. Furthermore, it is suggested that cycloadduct 3 has great anti-HIV potential because it exhibits lower binding energies than azidothymidine (AZT) in the docking studies of cycloadducts 3 and 4 amongst a primary HIV-1protein (1A8O plus 5W4Q).

Divergent Chemo‐ and Biocatalytic Route to 16β‐Methylcorticoids: Asymmetric Synthesis of Betamethasone Dipropionate, Clobetasol Propionate, and Beclomethasone Dipropionate

Abstract16β‐Methylcorticoids are among the most important glucocorticoid steroids for the treatment of various dermatological disorders, respiratory infections, and other allergic reactions elicited during inflammatory responses of the human body. Betamethasone dipropionate, clobetasol propionate, and beclomethasone dipropionate are particularly noteworthy for their synthetic intractability. Despite five decades of research, these 16β‐methylcorticoids have remained challenging synthetic targets owing to insurmountable issues of reactivity, selectivity, and cost efficiency associated with all previously explored strategies. We herein report our practicability‐oriented strategy toward the unified stereoselective synthesis of 16β‐methylcorticoids in 12.6–14.0 % overall yield from commercially available 9α‐hydroxyandrost‐4‐ene‐3,17‐dione (9α‐OH‐AD). In this approach, the chiral C16β‐Me and C17α‐OH groups of the corticosteroid D ring were installed via a substrate‐controlled diastereo‐ and enantioselective Mn‐catalyzed oxidation‐reduction hydration of Δ4,9(11),16‐triene‐3,20‐dione. The C1−C2 double bond of the corticosteroid A ring was constructed using an unprecedented engineered 3‐ketosteroid‐Δ1‐dehydrogenase (MK4‐KstD)‐catalyzed regioselective Δ1‐dehydrogenation of Δ4,9(11)‐diene‐3,21‐dione. This strategy provides a general method and a key precursor for the divergent synthesis of a variety of glucocorticoids and related steroidal drugs.

Geometrical Optimization and Natural Bond Orbital Analysis of Relevant Structures in the Diastereoselective Cuprate Conjugate Addition Reaction of α,β-Unsaturated Lactams using Density Functional Theory

In this study, density functional theory calculations at the wB97XD/Def2TZVPP level were performed to analyze the mechanism underlying the cuprate conjugate addition reaction of α,β-unsaturated lactams. The calculation results were well-aligned with those obtained experimentally–the keto-aminal and aldo-aminal, i.e. 2 and 1a, yield the syn- and anti-products, respectively. The diastereoselectivity reversal originates from the small differences in the structure of the reactants. The pyramidalization and C7N3C2 angle between the aminal carbon, nitrogen and carbonyl carbon are large in 2. The dihedral angle of the aminal oxygen, aminal carbon, nitrogen and carbonyl carbon, O8C7N3C2, is closer to 180º in 2 than in 1a. The NBO analysis revealed string interactions between the lone pair of N3 and carbonyl π*(O1–C2) bond. These results validate the assumption—the planarity around nitrogen in molecule 2 increases the nucleophilicity of the carbonyl oxygen, thereby driving the reaction between molecule 2 and trimethylsilyl chloride (TMSCl), which yields a siloxyiminium cation 5b and this 5b propels the syn addition of dimethylcuprate, leading to the formation of complex 7. The π(C5–C6) (HOMO) and π*(C2–N3) (LUMO) interactions in the siloxyiminium cation explain the increased C5–C6 double bond electrophilicity. The aldo-aminal 1a directly reacts with dimethylcuprate under steric control and yields the anti complex 6a, whose π character is stronger than that of the syn complex 7 and this weak π characteristics of 7 increases its stability to compensate for the trimethylsilyl disturbance. The bicyclic α,β-unsaturated lactam 8 does not contain aminal oxygen and thus remains unreactive during the cuprate conjugate addition reaction. Moreover, its pyramidalization is higher than that of the keto-aminal 2 and its dihedral angle of C8C7N3C2 is closer to 180º. Finally, a thermodynamic anti product is obtained, which is more stable than the syn- product because of less torsional strain.

(E)-3-(1,3-Diphenyl-1H-pyrazol-4-yl)-1-(thia-zol-2-yl)prop-2-en-1-one.

In the title mol-ecule, C21H15N3OS, the C5=C6 double bond in the central enone group adopts a trans configuration. The dihedral angle between planes of the thia-zole and pyrazole rings is 6.6 (2)°. In the crystal, pairs of C-H⋯O hydrogen bonds generate inversion dimers and another pair of C-H⋯N hydrogen bonds link the dimers into chains propagating along a-axis direction.

Exploring the Structural Importance of the C3=C4 Double Bond in Plant Alkaloids Harmine and Harmaline on Their Binding Interactions with Hemoglobin.

Harmine and harmaline are two structurally similar heterocyclic β-carboline plant alkaloids with various therapeutic properties, having a slight structural difference in the C3=C4 double bond. In the present study, we have reported the nature of the interaction between hemoglobin (Hb) with harmine and harmaline by employing several multispectroscopic, calorimetric, and molecular docking approaches. Fluorescence spectroscopic studies have shown stronger interaction of harmine with Hb compared to that of almost structurally similar harmaline. Steady-state anisotropy experiments further show that the motional restriction of harmine in the presence of Hb is substantially higher than that of the harmaline-Hb complex. Circular dichroism (CD) study demonstrates no conformational change of Hb in the presence of both alkaloids, but CD study in 1-cm cuvette path length also demonstrates stronger affinity of harmine toward Hb compared to harmaline. From the thermal melting study, it has been found that both harmine and harmaline slightly affect the stability of Hb. From isothermal titration calorimetry (ITC), we have found that the binding process is exothermic and enthalpy driven. Molecular docking studies indicated that both harmine and harmaline prefer identical binding sites in Hb. This study helps us to understand that slight structural differences in harmine and harmaline can alter the interaction properties significantly, and this key information may help in the drug discovery processes.

Peroxygenase‐Promoted Enzymatic Cascades for the Valorisation of Fatty Acids Front Cover: (ChemCatChem 11/2023)

The Front Cover shows enzymatic cascades for the valorisation of fatty acids with peroxygenase-catalysed hydroxylation as key step. Functionalisation of fatty acids generally relies on pre-existing functional groups such as C=C-double bonds. In their Research Article, F. Hollmann and co-workers demonstrated the synthetic potential of a peroxygenase mutant AaeUPO for selective fatty acid oxyfunctionalisation. The primary products (i.e., hydroxy fatty acid (esters)) are interesting building blocks for lactone- and polyester synthesis. Furthermore, the ω-1 hydroxy fatty acid (esters) produced were transformed into alcohols, esters and amines via multi-enzyme cascades thereby paving the way for new fatty acid valorisation pathways. More information can be found in the Research Article by F. Hollmann and co-workers.

Degradation products of aflatoxin M1 (AFM1) formed by high voltage atmospheric cold plasma (HVACP) treatment

Cold plasma technology is a novel non-thermal technology that has shown promising results for food decontamination and improving food safety. This study is a continuation of a previous investigation of the treatment of AFM1-contaminated skim and whole milk samples by HVACP. Previous research has shown HVACP is effective in degrading aflatoxin M1 (AFM1) in milk. The goal of this study is to identify the degradation products of AFM1 after HVACP treatment in pure water. An HVACP direct treatment at 90 kV using modified air (MA65: 65% O2, 30% CO2, 5% N2) was performed for up to 5 min at room temperature on a 5.0 mL water sample in a Petri dish artificially contaminated with 2 μg/mL of AFM1. The degradants of AFM1 were analyzed and their molecular formulae were elucidated by using high-performance liquid-chromatography time-of-flight mass spectrometry (HPLC−TOF-MS). Three main degradation products were observed and based on mass spectrometric fragmentation pathways, chemical structures for the degradation products were tentatively assigned. According to the structure–bioactivity relationship of AFM1, the bioactivity of the AFM1 samples treated with HVACP was reduced due to the disappearance of the C8–C9 double bond in the furofuran ring in all of the degradation products.

Ferrate(VI) mediated degradation of the potent cyanotoxin, cylindrospermopsin: Kinetics, products, and toxicity

The presence of cylindrospermopsin (CYN), a potent cyanotoxin, in drinking water sources poses a tremendous risk to humans and the environment. Detailed kinetic studies herein demonstrate ferrate(VI) (FeVIO42−, Fe(VI)) mediated oxidation of CYN and the model compound 6-hydroxymethyl uracil (6-HOMU) lead to their effective degradation under neutral and alkaline solution pH. A transformation product analysis indicated oxidation of the uracil ring, which has functionality critical to the toxicity of CYN. The oxidative cleavage of the C5=C6 double bond resulted in fragmentation of the uracil ring. Amide hydrolysis is a contributing pathway leading to the fragmentation of the uracil ring. Under extended treatment, hydrolysis, and extensive oxidation lead to complete destruction of the uracil ring skeleton, resulting in the generation of a variety of products including nontoxic cylindrospermopsic acid. The ELISA biological activity of the CYN product mixtures produced during Fe(VI) treatment parallels the concentration of CYN. These results suggest the products do not possess ELISA biological activity at the concentrations produced during treatment. The Fe(VI) mediated degradation was also effective in the presence of humic acid and unaffected by the presence of common inorganic ions under our experimental conditions. The Fe(VI) remediation of CYN and uracil based toxins appears a promising drinking water treatment process.

Effects of anti-cyclooxygenases (COX-1 and COX-2), structure activity relationship, molecular docking and in silico ADMET of some synthesized chalcones

Purpose: To develop effective cancer chemopreventive and anti-inflammatory agents, a series of chalcones were prepared by reacting suitable aromatic aldehyde with appropriate acetophenones.
 Methods: Twenty-four synthesized chalcones (namely, 1 - 24) were assessed for their in vitro anti-cyclooxygenase-1 (COX-1) and anti-cyclooxygenase-2 (COX-2) activity in a COX catalyzed prostaglandin synthesis bioassay. Molecular docking was done to investigate the ligand-protein interactions, and selectivity on both enzymes. ADMET (absorption, distribution, metabolism, excretion, toxicity) modeling and software were also used.
 Results: The compounds inhibited both COX-1 and COX-2. Two compounds (3 and 19) demonstrated more marked COX-2 inhibition than compound 1. Indomethacin as a standard anti-cyclooxygenase shows unselective inhibition of 81.44 ± 6.5 and 91 ± 9.5, respectively. The in silico data revealed that a chalcone skeleton with C=O at 4-position, C2–C3 double bond and OH at 5-position are necessary properties for anti-cyclooxygenase effects. It was also revealed that the propenone moiety comprises of an appropriate scaffold which proposes a new acyclic 1,3-diphenylprop-2-en-1-ones with selective anti-COX effects. A molecular modeling investigations where these chalcones 1, 3 and 19 were docked in the active site of COX-2 depicted that the p-CH3 substituent on the C-4- phenyl ring A are oriented in the vicinity of the COX-2 secondary pocket Phe381, Gly526, Tyr385 and Val349.
 Conclusion: Based on the screening for oral bioavailability, in silico ADMET, and toxicity risk assessment, this study shows that these compounds could be a cornerstone for the development of new pharmaceuticals in the battle against COX-associated inflammatory disorders.

Screening bifunctional flavonoids of anti-cholinesterase and anti-glucosidase by in vitro and in silico studies: Quercetin, kaempferol and myricetin

Type 2 diabetes mellitus (T2DM) and Alzheimer disease (AD) are two independent non-infectious diseases, however, evidences demonstrate that insulin resistance (IR) directly affects the glucose metabolism of the central nervous system (CNS), ultimately leading to neurodegenerative disorders, such as AD. Therefore, developing anti-AD/-diabetes inhibitors with fewer side effects have become a focus of the public and pharmacologist. In this study, the inhibitory activities of 16 flavonoids and 3 standards (galantamine, donepezil hydrochloride and acarbose) on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase (αG) and α-amylase (αA) and their corresponding structure-activity relationships were studied by multiple methods. The results showed that, unlike the positive effect of hydroxyl group, methoxy group of flavonoids had a negative effect on the inhibitory activity of enzyme. Besides, the glycosylation of C3 and C7 significantly reduced the inhibitory effect of flavonoids, and the hydrogenation of C2 = C3 double bond also had a similar inhibitory effect. Hence, flavonols, especially quercetin, kaempferol and myricetin showed high anti-AChE/-BChE/-αG/-αA activities, and their activities had a highest correlation with their antioxidant activities, while catechin, epicatechin, and artemetin had low inhibitory activities. Furthermore, molecular docking further confirmed the C4′-OH, C5′-OH and C3–OH of flavonoids skeleton played an important role in the binding and interaction between flavonoids and enzymes. In conclusion, flavonoids with specific structures may be used as inhibitors of cholinesterase, αG and αA in the treatment and prevention of AD and T2DM.

Flavonoids as Antidiabetic and Anti-Inflammatory Agents: A Review on Structural Activity Relationship-Based Studies and Meta-Analysis.

Flavonoids are a group of naturally occurring polyphenolic secondary metabolites which have been reported to demonstrate a wide range of pharmacological properties, most importantly, antidiabetic and anti-inflammatory effects. The relationship between hyperglycaemia and inflammation and vascular complications in diabetes is now well established. Flavonoids possessing antidiabetic properties may alleviate inflammation by reducing hyperglycaemia through different mechanisms of action. It has been suggested that the flavonoids’ biochemical properties are structure-dependent; however, they are yet to be thoroughly grasped. Hence, the main aim of this review is to understand the antidiabetic and anti-inflammatory properties of various structurally diverse flavonoids and to identify key positions responsible for the effects, their correlation, and the effect of different substitutions on both antidiabetic and anti-inflammatory properties. The general requirement of flavonoids for exerting both anti-inflammatory and antidiabetic effects is found to be the presence of a C2–C3 double bond (C-ring) and hydroxyl groups at the C3’, C4’, C5, and C7 positions of both rings A and B of a flavonoid skeleton. Furthermore, it has been demonstrated that substitution at the C3 position of a C-ring decreases the anti-inflammatory action of flavonoids while enhancing their antidiabetic activity. Correlation is discussed at length to support flavonoids possessing essential pharmacophores to demonstrate equipotent effects. The consideration of these structural features may play an important role in synthesizing better flavonoid-based drugs possessing dual antidiabetic and anti-inflammatory effects. A meta-analysis further established the role of flavonoids as antidiabetic and anti-inflammatory agents.

Solar-driven semi-conductor photocatalytic water treatment (TiO2, g-C3N4, and TiO2+g-C3N4) of cyanotoxins: Proof-of-concept study with microcystin-LR

Cyanobacteria and their toxins are a threat to drinking water safety as increasingly cyanobacterial blooms (mass occurrences) occur in lakes and reservoirs all over the world. Photocatalytic removal of cyanotoxins by solar light active catalysts is a promising way to purify water at relatively low cost compared to modifying existing infrastructure. We have established a facile and low-cost method to obtain TiO2 and g-C3N4 coated floating photocatalysts using recycled glass beads. g-C3N4 coated and TiO2+g-C3N4 co-coated beads were able to completely remove microcystin-LR in artificial fresh water under both natural and simulated solar light irradiation without agitation in less than 2 h. TiO2 coated beads achieved complete removal within 8 h of irradiation. TiO2+g-C3N4 beads were more effective than g-C3N4 beads as demonstrated by the increase reaction rate with reaction constants, 0.0485 min−1 compared to 0.0264 min−1 respectively, with TiO2 alone found to be considerably slower 0.0072 min−1. g-C3N4 based photocatalysts showed a similar degradation pathway to TiO2 based photocatalysts by attacking the C6–C7 double bond on the Adda side chain.

Synthesis of Clionastatins A and B through Enhancement of Chlorination and Oxidation Levels of Testosterone

Comprehensive SummaryA full account of semisyntheses of polychlorinated marine steroids clionastatins A and B is described. We have developed a unique two‐stage chlorination‐oxidation strategy that enabled concise and divergent semisyntheses of clionastatins A and B in 16 steps from inexpensive testosterone. Key transformations in chlorination stage include (a) conformationally controlled, stereospecific dichlorination through an unusual β‐chloronium intermediate to install the diequatorial C1,C2‐dichloride; (b) C4‐OH directed C19–H oxygenation followed by challenging neopentyl chlorination to install the C19–Cl. The high oxidation level was constructed through (a) the desaturation at C6–C7 through one‐pot photochemical dibromination–reductive debromination; (b) regioselective anti‐Markovnikov oxidation of the C6–C7 double bond by photoredox‐metal dual catalysis to forge the B ring enone; (c) late‐stage desaturation with SeO2 to introduce C8–C9 double bond. Wharton transposition was used to forge the D‐ring enone, and thermodynamically driven epimerization secured the cis‐fused C/D ring system. Furthermore, we also provided a 14‐step approach to clionastatin A by optimizing the construction of the D‐ring enone with a dehydration‐oxidation sequence.