Nanophotosensitizing through Space Charge Transfer Assemblies of Pentacenequinone Derivative for 'Metal-free' Photoamidation Reactions.

The present study demonstrates the influence of small portion (20 %) of organic co-solvent (DMSO/THF/ACN/MeOH) in mixed aqueous media (80 % water) in controlling the size, quantum yield and life time of the through space charge transfer assemblies (TSCT) of pentacenequinone derivative (TPy-PCQ-TPy). Among various solvent systems [H2 O : DMSO (8 : 2), H2 O : THF (8 : 2), H2 O : ACN (8 : 2) and H2 O : MeOH (8 : 2)] examined, highly emissive (Φf =12 %) and nano-sized assemblies having long life time (3.11 ns) were formed in H2 O : DMSO (8 : 2) solvent system. The solvent dependent differences in the size and excited state properties of TPy-PCQ-TPy assemblies are reflected in their photosensitizing behaviour in different solvent systems. Backed by excellent photosensitizing properties, TPy-PCQ-TPy assemblies smoothly catalyse the photoamidation reactions between unactivated/activated aldehydes and secondary amine under mild reaction conditions (visible light irradiation, aerial atmosphere, room temperature) in H2 O : DMSO (8 : 2) solvent mixture. The as prepared assemblies of TPy-PCQ-TPy also exhibit high potential to catalyse the oxidation of benzyl alcohols to aromatic aldehydes, thus, generating a possibility to use aromatic alcohols as the starting material in photoamidation reactions. The real time application of TSCT assemblies has also been demonstrated in gram scale transformation of aromatic aldehydes to aromatic amides and photooxidation of benzyl alcohol to aromatic aldehyde.

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.

Scalable Total Synthesis of Acremolactone B.

Acremolactone B is a pyridine-containing azaphilone-type polyketide with herbicidal activity. We developed an aza-6π electrocyclization-aromatization strategy to construct the tetrasubstituted pyridine ring and achieved the first total synthesis of this molecule on a gram scale. A bicyclic intermediate was expeditiously prepared by using [2 + 2] photocycloaddition and chemoselective Baeyer-Villiger oxidation, which was further elaborated to a densely substituted aza-triene. An electrocyclization-aromatization cascade was exploited to forge the tetracyclic core of the natural product, and the side chain was introduced through diastereoselective acylation and reduction.

Photochemical Route for Synthesizing Atomically Precise Metal Nanoclusters from Disulfide.

Practical approaches to the synthesis of atomically precise metal nanoclusters are in high demand as they provide the structural basis for investigating nanomaterials' structure-property correlations with atomic precision. The Brust-Schiffrin method has been widely used, while the essential reductive ligands (e.g., thiols) limit the application of this method for synthesizing metal nanoclusters with specific frameworks and surface ligands. In this work, we developed a photochemical route for synthesizing atomically precise metal nanoclusters by applying disulfide, which is a widely available, stable, and environmentally friendly sulfur source. This method enables the construction of structurally diverse metal nanoclusters and especially features the synthesis of PhS-protected metal nanoclusters that were not easily achieved previously and the gram-scale synthesis. A reduction-oxidation cascade mechanism has been revealed for the photochemical route. This work is expected to open up new opportunities for metal nanocluster synthesis and will contribute to the practical applications of this kind of nanomaterial.

Mesoporous Mixed-Metal-Organic Framework Incorporating a [Ru(Phen)3]2+ Photosensitizer for Highly Efficient Aerobic Photocatalytic Oxidative Coupling of Amines.

[Ru(Phen)3]2+ (phen = phenanthroline) as a very classical photosensitizer possesses strong absorption in the visible range and facilitates photoinduced electron transfer, which plays a vital role in regulating photochemical reactions. However, it remains a significant challenge to utilize more adequately and exploit more efficiently the ruthenium-based materials due to the uniqueness, scarcity, and nonrenewal of the noble metal. Here, we integrate the intrinsic advantages of the ruthenium-based photosensitizer and mesoporous metal-organic frameworks (meso-MOFs) into a [Ru(Phen)3]2+ photosensitizer-embedded heterometallic Ni(II)/Ru(II) meso-MOF (LTG-NiRu) via the metalloligand approach. LTG-NiRu, with an extremely robust framework and a large one-dimensional (1D) channel, not only makes ruthenium photosensitizer units anchored in the inner wall of meso-MOF tubes to circumvent the problem of product/catalyst separation and recycling of catalysts in heterogeneous systems but also exhibits exceptional activities for the aerobic photocatalytic oxidative coupling of amine derivatives as a general photocatalyst. The conversion of the light-induced oxidative coupling reaction for various benzylamines is ∼100% in 1 h, and more than 20 chemical products generated by photocatalytic oxidative cycloaddition of N-substituted maleimides and N,N-dimethylaniline can be synthesized easily in the presence of LTG-NiRu upon visible light irradiation. Moreover, recycling experiments demonstrate that LTG-NiRu is an excellent heterogeneous photocatalyst with high stability and excellent reusability. LTG-NiRu represents a great potential photosensitizer-based meso-MOF platform with an efficient aerobic photocatalytic oxidation function that is convenient for gram-scale synthesis.

Scalable Syntheses and Biological Evaluation of Africane-Type Sesquiterpenoids.

Practical total syntheses of africane-type sesquiterpenoids were realized by reexamination of a divergent strategy employing optimized three-component coupling followed by ring-closing metathesis and substrate-controlled cyclopropanation. This sequential eight-step conversion provided Δ9(15) -africanene, a common bicyclo[5.3.0]decane intermediate for the syntheses of africane derivatives, in more than twice the yield as in the previous approach. The scalability and robustness of this improved synthetic route were confirmed by gram-scale preparation of Δ9(15) -africanene. In vitro cell-based assays of the synthesized africane-type sesquiterpenoids disclosed that ester-incorporating derivatives showed cytotoxic activity against HeLa cells. The effect of relative and absolute configuration of africane-9,15-diol monoacetates on the cytotoxicity against HeLa cells was also investigated.

Gram-Scale Synthesis of Nanosized Li3 HoBr6 Solid Electrolyte for All-Solid-State Li-Se Battery.

Rare earth (RE) based halide solid electrolytes (HEs) are recently considered as research hotspots in the field of all-solid-state batteries (ASSBs). The RE-based HEs possess high ionic conductivity, credible deformability, and good stability, which can bring excellent electrochemical performances for ASSBs. However, the conventional synthetic methods of RE HEs are a mechanochemical process and co-melting strategy, both approaches require expensive raw materials and sophisticated equipment. Therefore, a lot of research work is required to promote the preparation methods for these promising SSEs in ASSBs. Thus, a vacuum evaporation-assisted synthesis method is developed for the massive synthesis of HEs. The as-prepared Li3 HoBr6 (LHB) has a high lithium-ion conductivity close to the mS cm-1 level and the LHB-based Li-Se ASSBs can be assembled by cold pressing. Theoretical calculations have revealed that the Li migrations are highly preferred in Li3 HoBr6 owing to the low energy cost and high tolerance of stable structure. The tetrahedral and octahedral pathways are responsible for Li migrations in short and long ranges, respectively. The results show that the LHB-based Li-Se battery has good stability and rate performance, indicating that LHB has potential application in the field of ASSBs.

An efficient and concise synthesis of a selective small molecule non-peptide inhibitor of cathepsin L: KGP94.

KGP94 is a potent, selective, and competitive inhibitor of the lysosomal endopeptidase enzyme (Cathepsin L) currently in preclinical trials for the treatment of metastatic cancer, which is a leading cause of cancer-associated death. Herein, we report two new synthetic routes for synthesizing the target compound through four consecutive steps, using a Weinreb amide approach starting from a common 3-bromobenzoyl chloride. A key step in the approach is a coupling reaction of a readily available Grignard reagent with amide 4 to produce 6, a previously unreported coupling pattern. These new strategies offer an efficient and alternative approach to synthesis of target compound with an excellent overall yield.

Gram-Scale Synthesis of an Ultrastable Microporous Metal-Organic Framework for Efficient Adsorptive Separation of C2H2/CO2 and C2H2/CH4.

A highly water and thermally stable metal-organic framework (MOF) Zn2(Pydc)(Ata)2 (1, H2Pydc = 3,5-pyridinedicarboxylic acid; HAta = 3-amino-1,2,4-triazole) was synthesized on a large scale using inexpensive commercially available ligands for efficient separation of C2H2 from CH4 and CO2. Compound 1 could take up 47.2 mL/g of C2H2 under ambient conditions but only 33.0 mL/g of CO2 and 19.1 mL/g of CH4. The calculated ideal absorbed solution theory (IAST) selectivities for equimolar C2H2/CO2 and C2H2/CH4 were 5.1 and 21.5, respectively, comparable to those many popular MOFs. The Qst values for C2H2, CO2, and CH4 at a near-zero loading in 1 were 43.1, 32.1, and 22.5 kJ mol-1, respectively. The practical separation performance for C2H2/CO2 mixtures was further confirmed by column breakthrough experiments.

Ball-Milling Induced Debonding of Surface Atoms from Metal Bulk for Construing High-Performance Dual-Site Single-Atom Catalysts.

One of the most pressing challenges in single-atom catalysis is the manipulation of the coordination environment of central metals to maximize the catalyst performance. Herein, we fabricated a high-performance catalyst (Co-SNC) by introducing S into the neighboring position of the Co-N4 coordination. The developed ball-milling method enabled large-scale synthesis, that over 4.7 g of Co-SNC can be produced in one pot. In benzylamine coupling reaction, Co-SNC exhibited the highest conversion of 97.5 % with 99 % selectivity toward N-benzylidenebenzylamine in 10 h among various Co catalysts. Density functional theory calculations revealed the crucial role of S atoms, which serve as the active sites for O2 activation, leaving the Co atoms free to adsorb benzylamine. Consequently, the adsorption energies of O2 and benzylamine were significantly increased. Our strategy suggests a feasible approach to enhance catalytic performance by delicately integrating dual active sites into a single catalyst unit.

Determination of the Absolute Configuration of Bioactive Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones and Study of Their In Vitro Metabolic Profile.

In recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug candidates. Nevertheless, most studies are conducted for bioactivity assays, and little is known about their absorption, distribution, metabolism, and elimination (ADME) properties. To perform metabolic studies, the synthesis of the naturally occurring quinazolinone, fiscalin B (1), and its chloro derivative, 4-((1H-indol-3-yl)methyl)-8,10-dichloro-1-isobutyl-1,2-dihydro-6H-pyrazino[2,1-b]quinazoline-3,6(4H)-dione (2), disclosed as an antibacterial agent, was performed in a gram scale using a microwave-assisted polycondensation reaction with 22% and 17% yields, respectively. The structure of the non-natural (+)-fiscalin B was established, for the first time, by X-ray crystallography as (1R,4S)-1, and the absolute configuration of the naturally occurring fiscalin B (-)-1 was confirmed by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra as (1S,4R)-1. in vitro metabolic studies were monitored for this class of natural products for the first time by ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS). The metabolic characteristics of 1 and 2 in human liver microsomes indicated hydration and hydroxylation mass changes introduced to the parent drugs.

Gram-Scale Synthesis of High-Loading Single-Atomic-Site Fe Catalysts for Effective Epoxidation of Styrene.

Single-atomic-site (SAS) catalysts, a new frontier of catalysts, always show extremely high atom efficiency and unexpected catalytic properties. Herein, a pyrolyzing coordinated polymer (PCP) strategy is developed, which is facile and widely applicable in the synthesis of a series of SAS catalysts including SAS-Fe, SAS-Ni, SAS-Cu, SAS-Zn, SAS-Ru, SAS-Rh, SAS-Pd, SAS-Pt, and SAS-Ir. The as-obtained SAS catalysts can be easily synthesized at gram scale and the metal loading of SAS-Fe catalysts achieves a record value of 30 wt%, which meets the requirement of practical applications. Moreover, it is discovered that SAS-Fe catalysts show unprecedented catalytic performance for epoxidation of styrene using O2 as the only oxidant (yield: 64%; selectivity: 89%), while Fe nanoparticles and ironporphyrin are inactive. This discovery is believed to pave the way for exploiting the unparalleled properties of SAS catalysts and promoting their industrial applications.

A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.

Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells. N-Glycan chains are synthesized by the sequential action of glycosyl transferases in the Golgi apparatus. It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively. It has long been known that N-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1). Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions. Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 µM. It was confirmed that APPB inhibits N-glycosylation of ß-catenin at 2.5 nM concentration. A sharp difference between APPB and tunicamycin was that the hemolytic activity of APPB is significantly attenuated (IC50 > 200 µM RBC). Water solubility of APPB is >350-times greater than that of tunicamycin (78.8 mg/mL for APPB, <0.2 mg/mL for tunicamycin). A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low µM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations. In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models. We have refined all steps in the previously reported synthesis for APPB for larger-scale. This article summarizes protocols of gram-scale synthesis of APPB and its physicochemical data, and a convenient DPAGT1 assay. •Remember that the abstract is what readers see first in electronic abstracting & indexing services.•This is the advertisement of your article. Make it interesting, and easy to be understood.•Be accurate and specific, keep it as brief as possible.

Hedgehog pathway inhibitors of the acylthiourea and acylguanidine class show antitumor activity on colon cancer in vitro and in vivo.

Small series of acylguanidine and acylthiourea derivatives were synthesized in gram-scale and assayed for their ability to modulate the Hh signalling pathway. In vitro studies showed a low micromolar inhibitory activity toward tumor cell lines, while the oral administration revealed an excellent ADME profile in vivo. Compound 5 emerged as the most active and safe inhibitor of colon cancer cells both in vitro and in a xenograft mouse model. Based on these data, 5 could be prioritized to further development with the perspective of clinical studies.

Gram-Scale Preparation of Iron Oxide Nanoparticles with Renal Clearance Properties for Enhanced T1-Weighted Magnetic Resonance Imaging.

Extremely small-sized iron oxide nanoparticles (ESIONs) have been accepted as a potential alternative to gadolinium-based contrast agents for enhanced T1-weighted MR imaging. Recently developed zwitterion-coated ESIONs showed a high T1 contrast power and efficient renal clearing ability, but the tedious preparation steps that required high-cost, unfriendly experimental conditions and a sophisticated phase transition process would likely hinder their clinical translation. Herein, we present a one-pot gram-scale synthesis of zwitterion-capped ultrasmall iron oxide nanoparticles (ZUIONs). The nanoparticles have a core size as small as 3.7 nm and display high colloidal stability in various buffers. The r1 relaxivity of 2.4 mM-1 s-1 and r2/r1 ratio as low as 2.2 at 1.0 T guarantee their application as effective T1 MRI contrast agents. In vivo studies showed that ZUIONs could induce a significant contrast enhancement in blood pool and be eliminated from the body mainly through the renal excretion pathway. The combined advantageous features including facile preparation, excellent biocompatibility, strong T1 MRI contrast effect, appropriate circulation time, and renal clearable property would render ZUIONs attractive for practical applications.

A succinct access to ω-hydroxylated jasmonates via olefin metathesis.

In higher plants, jasmonates are lipid-derived signaling molecules that control many physiological processes, including responses to abiotic stress, defenses against insects and pathogens, and development. Among jasmonates, ω-oxidized compounds form an important subfamily. The biological roles of these ω-modified derivatives are not fully understood, largely due to their limited availability. Herein, a brief (two-step), simple and efficient (>80% yield), versatile, gram-scalable, and environmentally friendly synthetic route to ω-oxidized jasmonates is described. The approach utilizes olefin cross-metathesis as the key step employing inexpensive, commercially available substrates and catalysts.

Multigram-scale Synthesis of Enantiopure 3,3-Difluoroproline.

An efficient route for the synthesis of enantiopure 3,3-difluoroproline on multigram-scale is described herein. The deoxofluorination can be achieved with DAST on the corresponding racemic pyrrolidinone in good yield. Resolution of the racemate by crystallization with D- and L-tyrosine hydrazide provides both enantiomers of 3,3-difluoroproline in high yield and ee%.

Gram-Scale Aqueous Synthesis of Stable Few-Layered 1T-MoS2 : Applications for Visible-Light-Driven Photocatalytic Hydrogen Evolution.

Most recently, much attention has been devoted to 1T phase MoS2 because of its distinctive phase-engineering nature and promising applications in catalysts, electronics, and energy storage devices. While alkali metal intercalation and exfoliation methods have been well developed to realize unstable 1T-MoS2 , but the aqueous synthesis for producing stable metallic phase remains big challenging. Herein, a new synthetic protocol is developed to mass-produce colloidal metallic 1T-MoS2 layers highly stabilized by intercalated ammonium ions (abbreviated as N-MoS2). In combination with density functional calculations, the X-ray diffraction pattern and Raman spectra elucidate the excellent stability of metallic phase. As clearly depicted by high-angle annular dark-field imaging in an aberration-corrected scanning transmission electron microscope and extended X-ray absorption fine structure, the N-MoS2 exhibits a distorted octahedral structure with a 2a0 × a0 basal plane superlattice and 2.72 Å Mo-Mo bond length. In a proof-of-concept demonstration for the obtained material's applications, highly efficient photocatalytic activity is achieved by simply hybridizing metallic N-MoS2 with semiconducting CdS nanorods due to the synergistic effect. As a direct outcome, this CdS:N-MoS2 hybrid shows giant enhancement of hydrogen evolution rate, which is almost 21-fold higher than pure CdS and threefold higher than corresponding annealed CdS:2H-MoS2.