Concise Route Research Articles

Borylation via iridium catalysed C-H activation: a new concise route to duocarmycin derivatives.

The synthesis of the ethyl ester analogue of the ultrapotent antitumour antibiotic seco-duocarmycin SA has been achieved in eleven linear steps from commercially available starting materials. The DSA alkylation subunit can be made in ten linear steps from the same precursor. The route involves C-H activation at the equivalent of the C7 position on indole leading to a borylated intermediate 9 that is stable enough for peptide coupling reactions but can be easily converted to the free hydroxyl analogue.

Design, synthesis, and anti-cancer evaluation of C-14 arylcarbamate derivatives of andrographolide

In this study, we explored a concise and mild synthetic route to produce novel C-14 arylcarbamate derivatives of andrographolide, a known anti-inflammatory and anticancer natural product. Upon assessing their anti-cancer efficacy against pancreatic ductal adenocarcinoma (PDAC) cells, some derivatives showed stronger cytotoxicity against PANC-1 cells than andrographolide. In addition, we demonstrated one derivative, compound 3m, effectively reduced the expression of oncogenic p53 mutant proteins (p53R273H and p53R248W), proliferation, and migration in PDAC lines, PANC-1 and MIA PaCa-2. Accordingly, the novel derivative holds promise as an anti-cancer agent against pancreatic cancer. In summary, our study broadens the derivative library of andrographolide and develops an arylcarbamate derivative of andrographolide with promising anticancer activity against PDAC.

Easy Access to Phenanthridinones via Metal-Free Cascade Benzannulation and C-N Bond Formation.

A concise route for the synthesis of dihydrobenzo[j]phenanthridinones has been disclosed through an aryne annulation strategy under metal-free reaction conditions. The reaction involves multiple C-C and C-N bond cleavages/formations via Diels-Alder reaction, aromatization-driven C-N bond cleavage, and amide formation.

Practical gram-scale synthesis of bicyclol metabolites M2 and M3

Bicyclol, an innovative hepatoprotective drug, was approved by the Chinese National Medical Products Administration (NMPA) in 2001 to treat Hepatitis B and drug-induced liver injury. Two active metabolites of bicyclol have been identified as M2 and M3. To evaluate the impact on drug safety and efficacy of possible drug-drug interactions (DDIs) associated with these metabolites, a sufficient quantity of these metabolites is required. Herein, we report a concise novel route for the synthesis of M2 and M3 using the Suzuki-Miyaura coupling as the key step. Furthermore, we complete the gram-scale syntheses of M2 and M3.

Synthesis of Polycyclic Imidazolidinones via Cascade [3 + 2]-Annulation of β-Oxo-acrylamides with Cyclic N-Sulfonyl Imines.

An Et3N-catalyzed cascade [3 + 2]-annulation of β-oxo-acrylamides with cyclic N-sulfonyl ketimines or sulfamate-derived imines is developed under mild reaction conditions, which provides a concise and efficient route to access valuable sultam- or sulfamidate-fused imidazolidinone derivatives in good to excellent yields (80-95% yields) with excellent diastereoselectivities (>20:1 drs). The current protocol features atom economy, a transition-metal-free process, and broad functional group tolerance. Moreover, the asymmetric variant of the [3 + 2]-cycloaddition reaction was achieved in the presence of diphenylethanediamine or quinine-based bifunctional squaramide organocatalysts C-1 and C-11, giving the corresponding chiral polycyclic imidazolidinones in 68-90% yields with 25-94% ees and >20:1 drs in all cases.

Decarboxylative Allylation of Silanecarboxylic Acids Enabled by Organophotocatalysis.

Herein we present a visible-light-facilitated transition-metal-free allylic silylation reaction under mild conditions. This protocol is enabled by an inexpensive organophotocatalyst and provides efficient and concise synthetic routes to substituted allylsilanes, particularly from readily available allyl sulfones and stable silanecarboxylic acids as silyl radical precursors. Further investigations reveal that this strategy is also generally compatible with vinyl sulfones to access vinylsilanes. The silver catalytic system opens up an alternative entry to realize the decarboxylative allylation of silanecarboxylic acids.

Towards bioresource-based aggregation-induced emission luminogens from lignin β-O-4 motifs as renewable resources

One-pot synthesis of heterocyclic aromatics with good optical properties from phenolic β-O-4 lignin segments is of high importance to meet high value added biorefinery demands. However, executing this process remains a huge challenge due to the incompatible reaction conditions of the depolymerization of lignin β-O-4 segments containing γ-OH functionalities and bioresource-based aggregation-induced emission luminogens (BioAIEgens) formation with the desired properties. In this work, benzannulation reactions starting from lignin β-O-4 moieties with 3-alkenylated indoles catalyzed by vanadium-based complexes have been successfully developed, affording a wide range of functionalized carbazoles with up to 92% yield. Experiments and density functional theory calculations suggest that the reaction pathway involves the selective cleavage of double C-O bonds/Diels-Alder cycloaddition/dehydrogenative aromatization. Photophysical investigations show that these carbazole products represent a class of BioAIEgens with twisted intramolecular charge transfer. Distinctions of emission behavior were revealed based on unique acceptor-donor-acceptor-type molecular conformations as well as molecular packings. This work features lignin β-O-4 motifs with γ-OH functionalities as renewable substrates, without the need to apply external oxidant/reductant systems. Here, we show a concise and sustainable route to functional carbazoles with AIE properties, building a bridge between lignin and BioAIE materials.

B(C6F5)3-Catalyzed Intramolecular Hydroalkoxylation Deuteration Reactions of Unactivated Alkynyl Alcohols.

Using D2O as a deuterium source, a method for the deuteration of intra- and extra-cyclic methylene has been developed for cyclic ethers with moderate yield and excellent deuterium incorporation. This transformation features superb functional group tolerance in a wide range of alkynols. Notably, the critical factor to achieve high deuterium incorporation is determined by the hydrogen isotope exchange reaction of an unstable oxonium ion. This novel methodology provides an efficient and concise synthetic route to a number of valuable deuterated cyclic ethers that are often difficult to prepare with other methods.

Fully Refined Semisynthesis of the [FeFe] Hydrogenase H-Cluster.

[FeFe] hydrogenases contain a 6-Fe cofactor that serves as the active site for efficient redox interconversion between H2 and protons. The biosynthesis of the so-called H-cluster involves unusual enzymatic reactions that synthesize organometallic Fe complexes containing azadithiolate, CO, and CN- ligands. We have previously demonstrated that specific synthetic [Fe(CO)x(CN)y] complexes can be used to functionally replace proposed Fe intermediates in the maturation reaction. Here, we report the results from performing such cluster semisynthesis in the context of a recent fully defined cluster maturation procedure, which eliminates unknown components previously employed from Escherichia coli cell lysate and demonstrate this provides a concise route to H-cluster synthesis. We show that formaldehyde can be used as a simple reagent as the carbon source of the bridging adt ligand of H-cluster in lieu of serine/serine hydroxymethyltransferase. In addition to the actual H-cluster, we observe the formation of several H-cluster-like species, the identities of which are probed by cryogenic photolysis combined with EPR/ENDOR spectroscopy.

Butterfly-Shaped Dibenz[a,j]anthracenes: Synthesis and Photophysical Properties.

A strategy for the synthesis of dibenz[a,j]anthracenes (DBAs) from cyclohexa-2,5-diene-1-carboxylic acids is presented. Our approach involves sequential C-H olefination, cycloaddition, and decarboxylative aromatization. In the key step for DBA skeleton construction, the bis-C-H olefination products, 1,3-dienes, are utilized as substrates for [4 + 2] cycloaddition with benzyne. This concise synthetic route allows for regioselective ring formation and functional group introduction. The structural features and photophysical properties of the resulting DBA molecules are discussed.

Effects of chirp of the white-light continuum seed on the pulse characteristics of collinear femtosecond optical parametric amplifiers

The influence of the chirp of the white-light continuum seed on the pulse characteristics of femtosecond optical parametric amplifiers (OPAs) is studied. Here, we focus on collinear OPAs based on type-I phase-matched BBO crystals. By numerical simulations, we investigate the evolution of the pulse-width, spectral bandwidth and time-bandwidth-product (TBP) of the amplified signal pulses with respect to the chirp of the white-light continuum seed pulses. In particular, we show that by manipulating the white-light continuum seed pulses to be highly chirped, nearly transform-limited optical pulses can be directly obtained from OPAs, without requiring dispersion-compensation elements. Our study demonstrates that chirp management offers a concise and effective technical route for obtaining nearly transform-limited, narrowband optical pulses from femtosecond OPAs, which would benefit many applications, including nonlinear imaging and spectroscopy.

A concise chemoenzymatic total synthesis of neutral Globo-series glycosphingolipids Globo A and Globo B, and Forssman and para-Forssman antigens.

Globo A is a neutral Globo-series glycosphingolipid (GSL) that shows natural properties of a cytotoxicity receptor NKp44 binding ligand. The highly complex heptasaccharide glycan structure of GloboA combined with its biological profile provides a unique target for the development of a synthetic method to facilitate its bioactivity studies. Here, a concise chemoenzymatic route to the synthesis of Globo A and its α1,3-galactose-linked congener Globo B is reported. The key to success was the use of a synthetic azido β-Globo H sphingosine (Globo H-βSph) as an acceptor substrate and two glycosyl transferases, an α1,3-N-acetylgalactosaminyltransferase from Helicobactermustelae (BgtA) and a human blood group B α1,3-galactosyltransferase (h1,3GTB), for stereoselective construction of the terminal α1,3-GalNAc and α1,3-Gal linkages, respectively. The azido-Sph lipid sidechain is further elaborated by reduction and a chemoselective N-acylation to complete the total synthesis of the neutral Globo-series GSLs. In addition, the synthesis of Forssman and para-Forssman antigens were prepared. The strategy may be suitable for accessing other complex GSLs and related lipid-modified GSL derivatives.

Visible-Light-Induced, Palladium-Mediated Desaturation/Sulfonation Cascade To Access 4-Sulfonyltetrahydropyridine Scaffolds.

Herein, we report a visible-light-induced, palladium-catalyzed desaturation/sulfonation cascade, offering a concise route to a series of highly valuable 4-sulfonyltetrahydropyridine scaffolds from inexpensive and readily available piperidine derivatives with sodium sulfinates. The key to the success of this transformation is the well-designed sequence of palladium-mediated 1,5-hydrogen atom transfer/β-hydride elimination/allylic sulfonation process, which demonstrates the synthetic potentials for orchestrating synthetic events by rationally taking advantage of varied catalytic modes.

Enantioselective SN 2 Alkylation of Homoenolates by N-Heterocyclic Carbene Catalysis.

The functionalization of the β-carbon of enals with electrophiles is a signature umpolung reactivity of N-heterocyclic carbene (NHC)derived homoenolates. However, only a limited number of electrophiles are shown to be compatible, with most of them being π-electrophiles. In this study, the successful enantioselective β-alkylation of homoenolates is reported using Csp3 electrophiles through an SN 2 strategy. The protocol shows a broad scope regarding alkyl electrophiles, delivering good yields, and excellent enantioselectivities (up to 99% ee). It enables the installation of drug-like structural motifs in either enals or alkylating agents, demonstrating its potential as a valuable tool for late-stage modification. Furthermore, a concise synthetic route is presented to chiral pyrroloindoline-type skeletons. Preliminary mechanistic studies support a direct SN 2 mechanism.

Total synthesis of pyrrolo-azepine fused alkaloids: Aspastipuline, portulacatone and related alkaloids via TFAA mediated intramolecular Friedel-Crafts acylation

Aspastipulines and Portulacatone are pyrrolo-azepine containing alkaloids isolated from Asparagus stipularis forssk roots and Portulaca oleracea, respectively that have significant anticancer properties and moderate anti-inflammatory activities. Herein, we report the first total synthesis of five Pyrrolo-azepine containing aspastipuline, portulacatone and related alkaloids from a commercially available starting materials, ethyl 1H-pyrrole-2-carboxylate, via TFAA mediated intramolecular Friedel-Crafts acylation as a key step in concise route with good overall yield.

Synthesis of 4,6-disubstituted bicyclo[3.3.1]nona-3,6-dien-2-ones

Bicyclo[3.3.1]nonane system is an important structural motif observed in a diverse natural products. Here, we report a concise synthetic route exploiting aldol condensation reactions for construction bicyclo[3.3.1]nonane ring system. Our strategy employes cyclohex-2-enones bearing another carbonyl group in side chain as key structural unit. The reaction showed good results for substrates bearing electron-donating groups in aromatic substituents. Overall, the described synthesis of bicyclo[3.3.1]nona-3,6-dien-2-ones required 2 steps and only 2 building blocks (such as Mannich base and acetoacetic ester) to access desired bicyclic system.

Versatile Biocatalytic C(sp3 )-H Oxyfunctionalization for the Site- Selective and Stereodivergent Synthesis of α- and β-Hydroxy Acids.

C(sp3 )-H oxyfunctionalization, the insertion of an O-atom into C(sp3 )-H bonds, streamlines the synthesis of complex molecules from easily accessible precursors and represents one of the most challenging tasks in organic chemistry with regard to site and stereoselectivity. Biocatalytic C(sp3 )-H oxyfunctionalization has the potential to overcome limitations inherent to small-molecule-mediated approaches by delivering catalyst-controlled selectivity. Through enzyme repurposing and activity profiling of natural variants, we have developed a subfamily of α-ketoglutarate-dependent iron dioxygenases that catalyze the site- and stereodivergent oxyfunctionalization of secondary and tertiary C(sp3 )-H bonds, providing concise synthetic routes towards four types of 92 α- and β-hydroxy acids with high efficiency and selectivity. This method provides a biocatalytic approach for the production of valuable but synthetically challenging chiral hydroxy acid building blocks.

Versatile Biocatalytic C(sp3)−H Oxyfunctionalization for the Site‐ Selective and Stereodivergent Synthesis of α‐ and β‐Hydroxy Acids

AbstractC(sp3)−H oxyfunctionalization, the insertion of an O‐atom into C(sp3)−H bonds, streamlines the synthesis of complex molecules from easily accessible precursors and represents one of the most challenging tasks in organic chemistry with regard to site and stereoselectivity. Biocatalytic C(sp3)−H oxyfunctionalization has the potential to overcome limitations inherent to small‐molecule‐mediated approaches by delivering catalyst‐controlled selectivity. Through enzyme repurposing and activity profiling of natural variants, we have developed a subfamily of α‐ketoglutarate‐dependent iron dioxygenases that catalyze the site‐ and stereodivergent oxyfunctionalization of secondary and tertiary C(sp3)−H bonds, providing concise synthetic routes towards four types of 92 α‐ and β‐hydroxy acids with high efficiency and selectivity. This method provides a biocatalytic approach for the production of valuable but synthetically challenging chiral hydroxy acid building blocks.

Controllable pore size of super-hydrophobic magnetic core-shell nanospheres with dendritic architecture and their pore-dependent performances in oil/water separation

The fundamental properties of porous materials strongly rely on their pore sizes. Pore-size-dependent performances play significant roles in their applications like catalysis, adsorption, delivery, and so forth. In this work, a feasible pore-expanding approach has been successfully explored to control the pore size of magnetic core–shell nanospheres with dendritic architecture (Fe3O4@DMSNs). The size can be adjusted from ca. 10 nm to 25 nm and further to 60 nm in an unprecedented wide range. Further, a concise modification route has been adopted to endow Fe3O4@DMSNs particles with super-hydrophobic abilities by the usage of a long-chain silane (Fe3O4@DMSNs-OTES). The as-prepared nanospheres with magnetic response function can not only form magnetic liquid marbles (MLMs) easily, but also separate n-hexane in oil–water mixtures or oil-in-water emulsions rapidly and efficiently. However, the above three particles display certain differences in their basic properties (like pore volume) and application performances (like oil removal efficiency). Most importantly, Fe3O4@DMSNs-OTES with 60 nm pores exhibit the best super-hydrophobicity in contact angles of H2O and MLMs, Fe3O4@DMSNs-OTES with 25 nm pores possess the maximum adsorption capacity, while the ones with 10 nm pores show the quickest adsorption rate (removal efficiency). The relationship between the performances and the pore size has been thoroughly revealed and well deciphered by wettability theory (e.g., Cassie-Baxter equation) and surface tension theory. In a word, all Fe3O4@DMSNs-OTES hold promising potentials as candidates for the practical wastewater purification on the basis of their characteristics.

Self-supported vortex texture in 3D curved magnets

Magnetic textures in the self-supported nanostructure, such as vortex, are promising for magnetic hyperthermia therapy and spintronics due to their low remanent state and topological protection. These configurations emerge from energy minimization in confined systems, such as nanodisk or nanoparticles. There are many techniques used to confine these magnetic textures. However, the most robust, cheap, and reproducible is always sought. This work applies colloidal lithography to produce self-supported nanocaps with a vortex as the ground state. Firstly, we perform micromagnetic simulations to determine which diameters and thicknesses stabilize the vortex as a ground state on nanocaps. Secondly, we simulate the magnetization curves to find the conditions with the smallest remanent state and largest loop hysteresis curves area. Finally, we experimentally corroborate the vortex configuration ground state using electron holography and vibrating the sample magnetometer. In addition, we performed a dynamic simulation to investigate the gyrotropic modes of the vortex core. We present a concise route to the fabrication of scalable vortex magnetic nanocaps. Our results show that the magnetic nanocaps produced have a great potential for application in medicine, such as magnetic hyperthermia, and in spintronics, for spin-transfer torque nano-oscillators.