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Covering: 2006 to mid-2010 [ABSTRACT FROM AUTHOR]

Covering: 2004 to June 2010 [ABSTRACT FROM AUTHOR]

Covering: 2000 to June 2010 [ABSTRACT FROM AUTHOR]

Covering: January to December 2009. Previous review: Nat. Prod. Rep., 2010, 27, 1186 [ABSTRACT FROM AUTHOR]

Covering: January 2009 to September 2010 inclusive [ABSTRACT FROM AUTHOR]

Covering: 2009. Previous review: Nat. Prod. Rep., 2010, 27, 165 [ABSTRACT FROM AUTHOR]

Covering: up to late 2009 [ABSTRACT FROM AUTHOR]

Covering: up to 2009 [ABSTRACT FROM AUTHOR]

Covering: 1982 to 2009 [ABSTRACT FROM AUTHOR]

Covering: 2007 to 2009 [ABSTRACT FROM AUTHOR]

A hydrophobic silica dusting agent containing carbon black has been used with latent finger marks to demonstrate that the agent can act as an enhancing matrix to generate a simple method for detecting a range of drugs using surface assisted laser desorption/ionisation time-of-flight mass spectrometry (SALDI-TOF-MS) in positive ion reflectron mode. The dusting agent produces developed marks for locating/visualising the prints whilst also acting as a SALDI-TOF-MS enhancer that is equivalent to the standard matrix enhancer 2,5-dihydroxybenzoic acid. This method has been applied to the analysis of latent fingermarks for contact residues on fingers, and for detection of illicit drugs for both parent drugs and their metabolites. Analysis was performed by direct MS analysis of the pre-dusted fingermarks on the surface of a target plate and, following lifting using commercial tape, MS analysis of the lifted marks. When 19 commercial powders were used only three produced MS spectra but with intensities less than those produced with the new powder. The presence of the parent drug and its metabolites was confirmed using SALDI-TOF-MS-MS following high energy collision induced dissociation when characteristic and unique fragmentation patterns were observed in each case. The distribution of these compounds on fingermarks was subsequently demonstrated using commercially available imaging software. [ABSTRACT FROM AUTHOR]

The central proposition advanced herein is that complex target oriented synthesis, enabled by historic advances in methodology, has enormously expanded the scope of the possible. Accordingly, natural products, a proven long-term source of pharma discovery, re-emerge as potentially valuable elements for synthesis-driven pharma exploitation. [ABSTRACT FROM AUTHOR]

A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as nitidane from Heteromurus nitidus. [ABSTRACT FROM AUTHOR]

Quinones are valuable structural motifs found in numerous natural products and pharmaceuticals. In particular, p-benzoquinones are of great interest because of their ready availability and versatile reactivity. They can serve as good Michael acceptors and participate in many cycloaddition, nucleophilic addition and multicomponent reactions. However, the construction of polycyclic architectures with increased stereochemical features is another perspective of quinone chemistry. The present review summarizes the recent advances (2018–2023) in stereoselective annulation involving p-benzoquinones for the construction of fused, spiro and bridged/cage frameworks. In this regard, different types of annulations, such as [3+2], [3+3], [3+2+1], [4+2] and [2+2], are discussed for accessing diverse fused heterocycles in a stereoselective manner. Some novel annulation methods are reviewed for building spiro heterocycles and cage molecules. Most of the reactions described in this review are simple, providing quick formation of the desired products with high stereoselectivity. In this regard, typical reaction mechanisms are presented to understand how quinoidal scaffolds show variable reactivity towards reaction partners. [ABSTRACT FROM AUTHOR]

Both chromenone and pyrrolo[2,1-a]isoquinolines (containing ring-junction nitrogen) are privileged scaffolds in the field of synthetic as well as medicinal chemistry. These fused hybrid moieties are found to be present in diverse natural products like lamellarins and in many biomaterials. Here, we summarize some synthetic methodologies in connection with the synthesis of 2- and 4-chromenones fused to the five-membered ring of pyrrolo[2,1-a]isoquinolines in diverse orientations and their biological significance as reported in the relevant research articles. Several methods for the synthesis of various such fused compounds have been reported in the literature by way of construction of either pyrrole, pyridine, isoquinoline, coumarin (2H-chromen-2-one), 4H-chromen-4-one or more rings simultaneously by the use of eco-friendly classical methods or transition metal-catalyzed methods. [ABSTRACT FROM AUTHOR]

A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as alscholarine A from Alstonia scholaris. [ABSTRACT FROM AUTHOR]

The core skeleton syntheses of 3′H-spiro[cyclohexane-1,1′-isobenzofuran]-2,5-dien-4-one, and their derivatives (3a–3w) of spirobisnaphthalene urnucratins, plecmillins, and lignan kadsulignan, were explored using Suzuki–Miyaura coupling product biphenols as the precursors and intramolecular oxidative dearomatization with high-valence iodine reagent PIFA as the key step in 46–91% yields. A wide range of functional groups were tolerated. Then, using this strategy in combination with the Diels–Alder reaction, two skeleton molecules (5ah and 6d) of the natural products urnucratins and plecmillins were successfully constructed in 78% and 39% overall yields, which provides a potential methodology for the total synthesis of Type D spirobisnaphthalene urnucratins and other natural products with similar structures. [ABSTRACT FROM AUTHOR]

Herein, an operationally simple and mild protocol for defluorinative alkylation and arylation between thianthrenium salts and α-trifluoromethyl alkene with visible light to afford gem-difluoroolefins has been developed. The main feature of this method is avoiding the use of a metal photocatalyst, and an organic photocatalyst is unnecessary for the arylation reaction. In addition, thianthrene can also be recycled and transformed to thianthrenium salts without affecting the efficiency of these reactions. The protocol demonstrates excellent tolerance of functional groups and viable functionalization of late-stage natural products and pharmaceutically relevant molecules. [ABSTRACT FROM AUTHOR]

The properties of natural products can be significantly influenced by glycosylation, emphasizing the key role of glycosyltransferases (GTs) in this process. The pursuit of tailored GT catalysts to meet the demands of the glycosylation industry aligns with the principles of green chemistry. However, steering GT engineering towards the desired direction often requires substantial effort. Herein, we employ a comparative molecular dynamics approach to guide the engineering of GTs to alter their catalytic performances. Through comparing the structural flexibility and site-saturation mutagenesis of two GTs BarGT-1 with narrow substrate scope and BarGT-3 with wide substrate scope, the identified substitution K321P in C-loop 5 of BarGT-1 greatly expanded the substrate scope towards diverse pharmaceutically valuable substrates, thereby the catalytic efficiencies were remarkably improved (e.g., 52- and 244-fold for 4′- and 6-hydroxyflavone, kcat/KM). Further, phylogenetic analysis demonstrated that lysine was a highly conserved residue in the GTs within BarGT-1 branch, and its key roles in regulating the substrate scope were validated through site-saturation mutagenesis in two novel GTs, BsyGT (K321F) and BgoGT (K322W). Moreover, the corresponding substitutions G325R/D in C-loop 5 of BarGT-3 also served as switches to regulate the substrate profile of BarGT-3. Finally, through the utilization of BarGT-1 and K321P, we successfully regulated the synthesis of valuable liquiritigenin glycosides with minor effort. The comparative molecular dynamics approach provides insights into the structural dynamics of GTs, optimizes enzymatic processes, and facilitates precise enzyme engineering, offering a directed synthetic paradigm to produce valuable glycosides. [ABSTRACT FROM AUTHOR]

Indole structural motifs are ubiquitous in natural products, pharmaceuticals, agrochemicals and functional materials. The immense importance of the indole moiety, especially in the field of drug discovery, has fuelled continued attention in indole chemistry for over a century. In the recent past, a large number of metal-free methodologies have been developed apart from metal-catalyzed annulation processes. The present review focuses on recent (2019–mid-2023) efforts towards the construction of the indole core via transition-metal-free methods, which include acid-catalyzed, base-catalyzed, photochemical, electrochemical, iodonium-salt promoted, SOCl2/DMSO-mediated, uncatalyzed/thermally assisted and miscellaneous methods. The reactions described in this review mostly employed readily accessible starting materials, and inexpensive catalysts that are environmentally benign and easy to handle. In most cases, mechanistic aspects have also been highlighted for better understanding of the reaction pathways. Interestingly, some of the synthesized compounds mentioned in this review are potentially bioactive. [ABSTRACT FROM AUTHOR]

Cyclic peptides have become a powerful modality in drug development. Naturally isolated cyclic peptides such as phakellistatins have been found to have broad-spectrum bioactivity. In this paper, we have prepared an analog of phakellistatin 18, and tried to compare its bioactivity with that of our reported phakellistatin 2 analog. It was found that compound 1 derived from phakellistatin 18 showed inferior inhibiting ability compared to the phakellistatin 2 analog, similar to the phenomenon observed in the natural products (phakellistatin 2 presented stronger antitumor activity than that of phakellistatin18). We have performed molecular docking of the two analogs with the MDM2 protein using AutoDock Tools, which showed that the phakellistatin 2 analog presented stronger binding through a H-bond, providing an explanation for the bioactivity difference. [ABSTRACT FROM AUTHOR]

Covering: 1984 to end 2014 Using both library paper copies and modern electronic copies, every known, published, English-language journal paper that employs either countercurrent or centrifugal partition chromatography solvent systems for natural product purifications has been studied and the solvent systems classified in a comprehensive database. Papers were studied from the earliest found examples containing natural product separations in 1984 until the end of 2014. In total, 2594 solvent systems have been classified, of which 272 are gradient systems. To observe any trends or patterns in the data, the natural product solutes were divided into 21 classes and the solvent systems into 7 different types. The complete database, sorted according to natural product class, is available for download to assist separation scientists in future liquid–liquid chromatography purifications. [ABSTRACT FROM AUTHOR]

A novel photocatalytic [4+2] cyclization strategy was developed for the transformation of biomass furan into a unique and cage-like oxabicyclo[2.2.1]heptene molecular skeleton. This strategy also enabled a significant and efficient cyclization of furan with acrylate. It provides access to the common core shared by a range of biologically active natural products and medicines, such as cantharidin, palasonin, and OBHSA. [ABSTRACT FROM AUTHOR]

Phyllobilins, derived from the breakdown of chlorophyll in plants, are acyclic tetrapyrroles that bear the signature ring E of the parent macrocycle. Few synthetic studies have concerned members of this emergent class of natural products, which now number >70. A prior synthesis of southern rim structures relied on Knoevenagel and Nazarov reactions to construct a dipyrromethane bearing the annulated ring E. Here, the synthesis has been extended to linear tetrapyrroles containing ring E as well as an appended dicyanovinyl unit. The latter serves as an optical marker with clearly observable absorption near 400 nm, rendering all compounds yellow, orange or red, thereby facilitating isolation and reaction monitoring. Knoevenagel condensation was carried out with a DC half (gem-dimethyl-substituted dihydrodipyrrin-1-carboxaldehyde bearing a 9-carboethoxy group) and an AB half (dipyrromethane equipped with a β-ketoester at the 8-position and the dicyanovinyl group at the 1-position). The resulting propenone is blocked by the ester and dicyanovinyl groups from reactions at the respective pyrrolic termini. Subsequent Yb(OTf)3-catalyzed Nazarov reaction accompanied by unexpected prototropic rearrangement afforded the isolated phyllobilin (8) wherein conjugation shifted from the DC dihydrodipyrrin moiety to the CB southern rim, thereby resembling the conjugation of a native phyllolumibilin. The expected direct products of Nazarov cyclization, the cis and trans products (pre-8-cis , pre-8-trans) due to the configuration of substituents in ring E, were not observed. Calculations by density functional theory showed the stability order as 8 > pre-8-trans > pre-8-cis. Access to phyllobilin analogues may open opportunities for fundamental studies pertaining to the native constituents, which are germane to plant sciences, nutrition, and ecology. [ABSTRACT FROM AUTHOR]

N-Nitrosamines represent a class of bifunctional nitrogen-radical precursors, but their application potential remains largely unexplored. This study reports the highly atom-economical production of diverse α-oximino sulfonamides via direct photo-mediated radical relay oximinosulfonamidation of activated or unactivated alkenes with N-nitrosamines triggered by organic sulfide. N-Nitrosamines worked as bifunctional reagents in this transformation, simultaneously generating aminyl radicals and NO radicals. The organic sulfide was designed to act as a radical decaging agent as well as a source of sulfonyl. Its strong radical capturing ability and affinity for alkenes enable the rapid capturing of the aminyl radicals, thereby inhibiting the rapid recombination of radical pairs in the solvent cage. The synthesized oxime units could also be easily converted into other functional groups, leading to selective downstream transformations. The mild photodegradation reaction of harmful N-nitrosoamines showed high functional group tolerance and compatibility, facilitating the late-stage functionalization of natural products and drug molecules, expanding the biologically relevant chemical space. [ABSTRACT FROM AUTHOR]

Silver(I) pentafluorobenzoate (1) possesses an atypical solubility for a silver(I) carboxylate, demonstrating solubility in a range of etheric and aromatic solvents. This versatile solubility has been probed crystallographically by single-crystal X-ray diffraction (SCXRD) due to the myriad of solid-state structures that were isolated from a variety of solvents, providing insights into how 1 can be utilised as a reuseable crystallisation aid. This potential as a reuseable 'catch-and-release' agent to obtain the solid-state structures of liquid natural products was screened with the racemic dihydrocarvone, achiral eucalyptol, and the chiral R-carvone, and found to be viable. The results of these screenings demonstrated improved crystallographic outcomes than other prior attempts utilising different methodologies (e.g., encapsulation). [ABSTRACT FROM AUTHOR]

A hydrosulfonylation reaction of unactivated alkenes with sulfinic acids was realized under light irradiation. This reaction features photocatalyst- and additive-free conditions. A diverse set of unactivated alkenes can be transformed into alkyl-substituted sulfones with good yields and anti-Markovnikov regioselectivity. The present protocol was amenable to gram-scale synthesis, as well as late-stage modification of drugs and natural products. Preliminary mechanistic studies on UV-visible light absorption suggested the key role of sulfinic acid as a light-absorbing species. DFT calculations also shed light on the mechanism of this reaction, which may involve a radical chain pathway. [ABSTRACT FROM AUTHOR]

Although defluorinative functionalization of trifluoromethylarenes has been studied by several research groups, different kinds of catalysts are required accordingly based on specific substrate families to obtain the corresponding RCF2Ar compounds. Herein, we report a general photocatalytic approach for the selective hydrodefluorination (HDF) and defluoroalkylation (DFA) of ArCF3. Using electronically-different arenethiolates as photosensitizers, 88 α,α-difluoromethyl compounds were synthesized from a broad range of electronically-variable trifluoromethylarenes, including natural products and bioactive molecules. Our mechanistic studies uncovered photo-induced electron donor–acceptor (EDA) complexation followed by silane-assisted C–F bond activation. [ABSTRACT FROM AUTHOR]

Eight-membered ring skeletons are widely present in a variety of natural products and bioactive molecules. In particular, eight-membered nitrogen-heterocycles are compelling privileged structures for drug discovery, especially for challenging targets that are difficult to modulate using conventional small molecule screening libraries. However, the construction of eight-membered N-heterocycles is a formidable challenge in chemistry owing to unfavorable entropic and enthalpic effects. Thus, the development of novel strategies to access these scaffolds is highly desirable. In this review, we summarize the progress in the synthesis of eight-membered N-heterocycles in the past 20 years (1995–2023), with a focus on reaction mechanisms associated with typical reactions. We aim to inspire synthetic chemists to develop efficient strategies for the construction of eight-membered N-heterocycles. [ABSTRACT FROM AUTHOR]

Organoboron compounds have a wide-range of applications in synthetic methodologies, natural products, and bioactive molecule synthesis. The sensitivity of boronic acid toward most synthetic reagents makes it necessary to introduce a protecting group before its utilization. Benchtop stable MIDA boronates have been found compatible with various common synthetic reagents which opens the doors for the synthesis of various small building blocks, natural products, and bioactive compounds. MIDA boronate compounds have been extensively utilized in Suzuki Miyaura coupling and Iterative cross-coupling reactions for the total synthesis of bioactive molecules and polymerization reactions. Different MIDA boronate compounds like vinyl, acyl, formyl, acrylic, and α-carbonyl MIDA boronates also act as novel synthetic building blocks for various synthetic transformations in organic synthesis. This paper summarizes the importance of MIDA boronate compounds in various aspects of organic chemistry. [ABSTRACT FROM AUTHOR]

A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as chlorfortunone A from Chloranthus fortunei. [ABSTRACT FROM AUTHOR]

5-Hydroxymethylfurfural (HMF) is a natural product derived from the degradation of sugars in e.g. milk, honey and raisins. Recent studies have shown that this compound has several beneficial physiological effects including antioxidant activity. In the present paper, the antiradical properties of 5-HMF were systematically investigated by using the M06-2X/6-311++G(d,p) model chemistry in the gas phase, in water solution and, for a lipid-mimetic environment, in pentyl ethanoate solvent. The thermodynamic and kinetic modelling of the reactions of 5-HMF with a range of reactive oxidative species revealed that 5-HMF scavenges HO˙ and HOO˙ radicals. The overall rate constants for the HO˙ radical scavenging in the gas phase and water and pentyl ethanoate solvents are 2.39 × 1012, 5.92 × 109 and 5.28 × 109 M−1 s−1, respectively, whereas those for the HOO˙ radical scavenging in these environments are low with k = 1.27 × 102, 12.1 and 5.48 M−1 s−1, respectively. The radical adduct formation mechanism plays an important role in the reactions of 5-HMF with HO˙ radicals in all of the studied media. [ABSTRACT FROM AUTHOR]

A suitable drug delivery strategy for metallodrugs is as significant as the strategies adopted for an efficient metallodrug design. In this study, piperlongumine, which is isolated from long pepper, is coordinated with a Ru(II)-p-cymene moiety to obtain an organoruthenated complex containing the natural product (Ru(pip)). The isolated complex shows higher cytotoxicity in MCF-7 breast cancer cells than in THP-1 leukemia and HepG2 liver cancer cells. The IC50 value of the complex in non-cancerous HEK-239 cells is also almost equal to that in MCF-7 cells. Next, with an aim to modulate the antiproliferative activity of Ru(pip) using a drug delivery strategy, the complex is loaded into mesoporous silica nanorods (MSNRs), which have a higher surface area than spherical silica nanoparticles. Furthermore, the outer surface of the loaded nanorods is covered with a polydiacetylene-lipid (PL) hybrid bilayer. Given the unique optical properties of polydiacetylene, the PL coating modifies non-fluorescent MSNRs into red-emissive particles (PL-Ru(pip)@MSNRs), which can be useful for diagnostic applications. The release profile studies reveal that the ene-yne conjugation in the PL coating ensures the sustained release of the complex from nanoparticles in both physiological and simulated cancer cell media. While Ru(pip) exhibits both necrotic and apoptotic modes of cell death, PL-Ru(pip)@MSNRs preferably induce the apoptotic mode of cell death in MCF-7 and THP-1 cells. Also, the nanoformulation exhibits a higher percentage of cell cycle arrest in the G0/G1 phase than Ru(pip), as measured by flow cytometry analysis. In contrast, the in vitro antioxidant potency of the complex is decreased after being loaded into PL-coated silica nanoparticles. [ABSTRACT FROM AUTHOR]

Functionalization of C(sp3)–H bonds should greatly benefit the synthesis of natural products and pharmaceuticals. One of the greatest challenges is to develop new synthetic strategies for industrial applicability. Herein we report an electrochemical method for the chlorination/bromination of tertiary and secondary benzylic C(sp3)–H bonds. This method tolerates many functional groups. Moreover, this reaction can be easily scaled up to 100 grams without losing its efficiency. [ABSTRACT FROM AUTHOR]

YEATS domains have been recently identified as novel readers of histone lysine acylation. Increasing evidence has revealed that dysregulated interactions between YEATS domains and histone lysine acylation are associated with human disease, suggesting the therapeutic potential of YEATS domain inhibition. The inhibitors targeting the YEATS domains of AF9, ENL, and GAS41 have been developed, while the YEATS2 YEATS domain inhibitors have not been reported so far. In this study, we have identified potential YEATS2 YEATS domain inhibitor candidates by integrating multiple computational approaches. Structure-based and ligand-based virtual screening was performed, and a total of 101 small molecule ligands were found from ZINC Natural Products, Enamine Advanced and Enamine HTS with affinity >−8.5 kcal mol−1. Structure-based drug design (SBDD) and ligand-based drug design (LBDD) strategies were used to conduct three rounds of molecular optimization based on the interaction between the small molecule ligands and the YEATS2 YEATS domain, and three groups of optimized molecules with better binding affinity were finally selected. The optimized compounds op2-1, op2-6, op3-5, and op3-6 were selected for molecular dynamics (MD) simulation studies to examine the interaction and stability of the best predicted conformation of the protein–ligand complex (MM/GBSA, −49.85 to −73.21 kcal mol−1). This study identifies the dominant molecular fragments and interaction modes that bind to various parts of the YEATS2 YEATS domain. Taken together, our study provides a starting platform for the development of highly active and selective inhibitors for the YEATS2 YEATS domain and the study of their mechanism of action in the future. [ABSTRACT FROM AUTHOR]

A general catalytic protocol for the halodecarboxylation of aliphatic carboxylic acids via ligand-to-metal charge transfer (LMCT) is presented. This conversion is capable of transforming primary, secondary, and tertiary alkyl acids into the corresponding bromo-, iodo- and chloroalkanes using water as a solvent under an air atmosphere. The broad range of substrate scope, the use of a green solvent, and the ability to derivatize drug molecules and natural products offer a new prospect for decarboxylative halogenation reactions. [ABSTRACT FROM AUTHOR]

Five coumarin derivatives, able to coordinate Fe(iii) and exhibit a ratiometric and turn-on fluorescence response, were prepared and tested. The derivative with the –OCH3 substituent exhibited a high fluorescence enhancement in the presence of Fe(iii), Ga(iii), Au(iii) and Y(iii). Thanks to the higher stability of the Fe(iii) complexes, this molecule could be proposed as a selective fluorescent sensor for the detection of Fe(iii) in CH3CN and CH3CN : H2O (1 : 1, v/v) solutions, showing a linear response up to 35.0 μM Fe(iii) concentration and a limit of detection of 2.4 μM Fe(iii) concentration. The fluorescence response towards this ion was also tested on a solid surface with a simple cellulose paper-strip test. The peculiarity of the proposed sensor lies in its easy and low-cost synthesis, relevant ratiometric response and, since it is derived from a natural product, low impact on the environment and its organisms. [ABSTRACT FROM AUTHOR]

Herein, a straightforward and regioselective avenue to angular azolo[1,5-a]pyrimidine derivatives via the three-component cyclization of aldehydes and α-aminoazoles with cycloketones is presented. The initiation of the condensation reaction between aldehydes and amines is key to the achievement of high regioselectivity in this process through bypassing the general aldol condensation of aldehydes and ketones. It is worth noting that this simple and scalable protocol was successfully applied to the derivatization of several structurally diverse natural products and pharmaceuticals. [ABSTRACT FROM AUTHOR]

The comprehensive utilization of agro-industrial residues poses a persistent global challenge. Microbial fermentation is an efficient way to convert agro-industrial residues into valuable products. Trichoderma reesei is a traditional cellulase and other protein producer using agro-industrial residues as substrates. The potential of T. reesei as a chassis to produce small natural products remains untapped. Here, we successfully employed T. reesei to efficiently synthesize different terpene types. To optimize the chassis for metabolite synthesis, we deleted major (hemi-)cellulase genes along with the global regulator Lae1 to improve the efficiency of secondary metabolite biosynthesis, and overexpressed the constitutively activated transcriptional factor XYR1A824V in MC3 (a uridine auxotrophic strain derived from T. reesei Rut-C30) to alleviate glucose repression. Through glucose, lactose, and corn steep as substrates, the production of ophiobolin F using the modified chassis was increased to 1187.06 mg L−1 in shake flask fermentation and up to 3072.45 mg L−1 under fed-batch fermentation. We further demonstrated the versatility of the Δlae1::xyr1/MC3-Δ10 chassis by successfully producing other fungal and plant terpenes. Collectively, our results demonstrated the potential of the Reducing Outflow and Broadened Upstream Substrate Type (ROBUST) T. reesei chassis for efficient terpene production utilizing agro-industrial residues, with important implications for terpene biosynthesis and sustainable biofabrication. [ABSTRACT FROM AUTHOR]

A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as chlorahupetone A from Chloranthus henryi var. hupehensis. [ABSTRACT FROM AUTHOR]

The dehydrogenative [4 + 2] annulation is a step- and atom-economical way to construct benzo-fused six-membered rings which are prevalent in natural products, pharmaceuticals and agrochemicals. Herein, we disclosed a visible-light induced dehydrogenative [4 + 2] annulation of benzothioamides and alkynes, which was performed under mild aerobic conditions and catalyzed by the metal-free heterogeneous photocatalyst graphitic carbon nitride (g-C3N4). The heterogeneous photocatalysis proceeded smoothly with simple operation and under mild conditions and gave a variety of isothiochromenes in good yields. g-C3N4 displays excellent stability and recyclability for the photochemical reaction. The detailed mechanistic studies revealed that g-C3N4 promoted the formation of a sulfur centered radical under visible-light irradiation via a single electron transfer process. The radical intermediate further mediated a [4 + 2] annulation with alkynes to produce isothiochromenes. [ABSTRACT FROM AUTHOR]

Quinolines are important building blocks for the synthesis of natural products and pharmaceuticals. In comparison with classical methods, dehydroaromatization of 1,2,3,4-tetrahydroquinolines has emerged in recent years as an efficient and straightforward way to access quinolines due to its high atom economy and sustainability. However, existing chemical methods suffer from the use of transition metal catalysts and harsh reaction conditions. Herein, we report a novel biocatalytic route for the efficient oxidative dehydrogenation of 1,2,3,4-tetrahydroquinolines employing monoamine oxidase from Pseudomonas putida KT2440 (PpMAO) with molecular oxygen, affording the corresponding quinolines with moderate to excellent yields (up to 99%) combined with the adjustment of the microenvironment for deprotonation and the supplied amount of molecular oxygen. Unlike other common one-step aromatizations of N-heterocycles, mechanism studies have suggested that PpMAO-catalyzed aromatization involves at least two-step C–N bond dehydrogenation reactions. The first step is the formation of an imine intermediate catalyzed by enzymes, followed by enzyme-mediated aromatization in the second step. Furthermore, preparative-scale biotransformation of tetrahydroquinolines was successfully demonstrated with good isolated yields (up to 95%). This system not only provided an efficient and facile method for the synthesis of quinolines under mild conditions but also enriched the redox biocatalytic approaches to N-heterocycles. [ABSTRACT FROM AUTHOR]

Chiral 3-substituted tetrahydroquinolines are important structural units in natural products and biologically active compounds. However, the efficient asymmetric synthesis of these interesting scaffolds is still a challenging task. Herein, a general chemo-enzymatic approach for the asymmetric synthesis of chiral 3-substituted tetrahydroquinolines with excellent enantioselectivity has been developed by combining biocatalysis and the Buchwald–Hartwig cross-coupling reaction, offering an effective method for the construction of chiral 3-substituted tetrahydroquinolines from simple aldehydes and allylamine. The key step involves a one-pot ene reductase (ERED)/imine reductase (IRED) cascade to convert α,β-unsaturated aldehydes to (S)-N-(3-aryl-2-methylpropyl) prop-2-en-1-amines with excellent ee values (97 to >99%), thus having addressed the issue of racemization of the intermediate via the synergistic effect of the bienzymatic cascade. This method was successfully used for the preparation of the key intermediate of the antithrombotic drug (21S)-argatroban on a gram scale. [ABSTRACT FROM AUTHOR]

Analysis of the effect of steric compression on the chemical shifts of carbons (13C NMR) in diastereoisomers is an accessible strategy for assigning the absolute configuration of secondary alcohols. Here we take advantage of such chemical shift differences and establish a validation protocol to assign the absolute configuration of secondary alcohols in natural products. The two enantiomers of methyl-1-(chloromethyl)-5-oxopyrrolidine-2-carboxylate are used as derivatizing agents to treat separately a secondary alcohol producing two diastereoisomeric derivatives. These derivatives exhibit clear 13C NMR differences only at four carbons: first at the stereogenic oxygenated carbon and methylene of the chiral assistant with a deshielding effect up to 3 ppm, and a shielding effect for the α carbons to the stereogenic centre. With the results obtained from a 1D NMR 13C spectrum, we were able to establish the absolute stereochemistry of the asymmetric centre beyond the concept of anisotropy. The observed changes in chemical shifts correlate well with the results obtained by the GIAO method applying the B3LYP/6-311+(2d,p) theoretical model to calculate the NMR shielding tensors of the diastereoisomeric derivatives. Furthermore, the steric compression effect was observed as well by 1H NMR at the methylene of the pyroglutamic moiety, since the magnitude of its geminal coupling constant is directly influenced by the stereochemistry of the secondary alcohol, thus, confirming the stereochemistry assignation of the asymmetric carbon. [ABSTRACT FROM AUTHOR]

A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as longisglucinol A from Hypericum longistylum. [ABSTRACT FROM AUTHOR]

Currently, extraction process optimization is generally based on a few features, regardless of their different changing trends and the panoramic view of the extraction process. Comprehensive evaluation and understanding is hard to establish due to the small number of experiments. Here, machine learning-assisted optimization is demonstrated for better understanding the complex extraction process based on data from an orthogonal experimental design (OED). From two perspectives of panoramic characteristics and specific characteristics, several observations are adopted to evaluate the performance of the extraction process, including quantitative 1H NMR, HPLC fingerprint, molecular weight, yield of dry extract and content of components. The close relationship between influencing factors and the extraction performance is described by grey relation analysis. With the help of radial basis function neural network (RBFNN), a nonlinear fitting regression equation is developed for every observation and influencing factor. A genetic algorithm is then introduced for multi-objective optimization and Pareto fronts are obtained. To select the best combination of water extraction process and ethanol extraction process, a list of the combinations of Pareto front points from those extraction processes is formed and ranked using CRITIC-TOPSIS. Finally, the ideal extraction is characterized by molecular weight, monosaccharide composition and UHPLC-MS/MS. With the verification between OED experiments and machine learning, the changing rates of all observations range from 1.33% to 30.11%, which confirms that machine learning-assisted optimization gives better performance than conventional OED. Molecular weight could range from 61.5~594.9 kDa with some are over measuring range, furthermore mannose and glucose are the most abuntant monosaccharides of the polysaccharide from ideal extraction. 160 components are identified via UHPLC-MS/MS as well. In conclusion, ML is a powerful tool for predicting and understanding extraction processes, thus accelerating the development of eco-friendly extraction processes. [ABSTRACT FROM AUTHOR]

Here, we demonstrate the first example of natural product harmaline and its derivatives serving as useful N–C synthons in formal [3+2] cycloadditions with isothiocyanates for the construction of a library of spiropolycyclic harmaline-based hybrids containing two adjacent quaternary stereocentres. These products were smoothly afforded in up to 90% yield, 20 : 1 dr with Et3N as the catalyst under mild conditions. To the best of our knowledge, this also represents the first example of the synthesis of natural product harmaline-based spiropolycyclic scaffolds, and expands the chemical space of biologically significant harmaline derivative species. The newly synthesized structurally diverse compounds were evaluated for their in vitro anticancer activities. These studies indicate that some compounds displayed good anticancer activity against three tumor cells (A549, K562, and PC-3). Among them, compound 3cb displayed the best activity when applied to A549, which is similar to that of cisplatin. Preliminary mechanistic studies indicate that compound 3cb induces apoptosis in A549 cells through a caspase-dependent pathway. These results show that compound 3cb can be prepared as a good lead for drug development. [ABSTRACT FROM AUTHOR]

The formation of C-S bonds using cheap, stable and odorless sulfonyl chlorides and widely sourced and less toxic alcohols with the assistance of ADDP is reported. This method is suitable for a broad substrate scope and tolerates a broad range of functional groups. Additionally, our protocol provides a green and convenient methylating method utilizing methanol or methanol-d4 and allows trideuteromethylthiolation with sulfonyl chlorides. This method can be applied for the late-stage diversification of natural products and drug analogs. [ABSTRACT FROM AUTHOR]

An electrochemical method for the direct synthesis of 1,2-diester derivatives from abundant and readily available olefins and carboxylic acids is described. The method is applicable to a variety of aromatic/aliphatic olefins and (hetero) aromatic/aliphatic carboxylic acids to produce the corresponding 1,2-diesters in moderate to good yields under mild and environmentally friendly conditions without the need for metals, catalysts, oxidants, sacrificial reagents and additives. The only by-product of the reaction is hydrogen released at the cathode, so this method is clean and highly atom- and step-economical. The diesterification of drugs and natural products further demonstrates the synthetic utility of the method. [ABSTRACT FROM AUTHOR]

Sustainable production of chemicals from renewable non-food biomass has become a promising alternative to overcome environmental issues caused by our heavy dependence on fossil resources. Systems metabolic engineering, which integrates traditional metabolic engineering with systems biology, synthetic biology, and evolutionary engineering, is enabling the development of microbial cell factories capable of efficiently producing a myriad of chemicals and materials including biofuels, bulk and fine chemicals, polymers, amino acids, natural products and drugs. In this paper, many tools and strategies of systems metabolic engineering, including in silico genome-scale metabolic simulation, sophisticated enzyme engineering, optimal gene expression modulation, in vivo biosensors, de novo pathway design, and genomic engineering, employed for developing microbial cell factories are reviewed. Also, detailed procedures of systems metabolic engineering used to develop microbial strains producing chemicals and materials are showcased. Finally, future challenges and perspectives in further advancing systems metabolic engineering and establishing biorefineries are discussed. [ABSTRACT FROM AUTHOR]