A Concise Synthesis of (2R,6R)-Hydroxynorketamine.

A concise synthesis of (2R,6R)-hydroxynorketamine was accomplished in eight steps, starting from commercially available materials. This synthesis features a cerium chloride-enhanced Stork-Danheiser reaction, an asymmetric reduction of ketone by the Corey-Bakshi-Shibata reaction, a signature Overman rearrangement, and a facial selective dihydroxylation of an electronically deficient olefin by RuCl3/NaIO4. The overall yield is 7.3% with 94.5% ee.

Synthesis of flavones via the Stork-Danheiser reaction.

A new method to access flavones in a convergent fashion has been developed, based on the Stork-Danheiser reaction. By this method, 4-methoxy coumarins are allowed to react with organolithium at low temperatures (-78 °C to -40 °C) and then acidic workup gives the desired flavones in 18-86% yields. This method features transition metal-free conditions, readily available starting materials, and simple operation. It is particularly efficient when rapid generation of B ring flavone derivatives is desired.

Strategies for total synthesis of bispyrrolidinoindoline alkaloids.

Covering up to 2021Complex cyclotryptamine alkaloids with a bispyrrolidino[2,3-b]indoline (BPI) skeleton are an intriguing family of natural products, exhibiting wide systematic occurrences, large structural diversity, and multiple biological activities. Based on their structural characteristics, BPI alkaloids can be classified into chimonanthine-type BPI alkaloids, BPI diketopiperazines, and BPI epipolythiodiketopiperazines. These intricate molecules have captivated great attention soon after their isolation and identification in the 1960s. Due to the structural complexity, the total synthesis of these cyclotryptamine alkaloids is challenging. Nevertheless, remarkable progress has been achieved in the last six decades; in particular, several methods have been successfully established for the construction of vicinal all-carbon quaternary stereocenters. In this review, the structural diversity and chemical synthesis of these BPI alkaloids were summarized. BPI alkaloids are mainly synthesized by the methods of oxidative dimerization, reductive dimerization, and alkylation of bisoxindole. The purpose of this review is to present overall strategies for assembling the BPI skeleton and efforts towards controlling the stereocenters.

Bisulfite-Free, Nanoscale Analysis of 5-Hydroxymethylcytosine at Single Base Resolution.

High-resolution detection of genome-wide 5-hydroxymethylcytosine (5hmC) sites of small-scale samples remains challenging. Here, we present hmC-CATCH, a bisulfite-free, base-resolution method for the genome-wide detection of 5hmC. hmC-CATCH is based on selective 5hmC oxidation, chemical labeling and subsequent C-to-T transition during PCR. Requiring only nanoscale input genomic DNA samples, hmC-CATCH enabled us to detect genome-wide hydroxymethylome of human embryonic stem cells in a cost-effective manner. Further application of hmC-CATCH to cell-free DNA (cfDNA) of healthy donors and cancer patients revealed base-resolution hydroxymethylome in the human cfDNA for the first time. We anticipate that our chemical biology approach will find broad applications in hydroxymethylome analysis of limited biological and clinical samples.

Bisulfite-free, base-resolution analysis of 5-formylcytosine at the genome scale.

Active DNA demethylation in mammals involves oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). However, genome-wide detection of 5fC at single-base resolution remains challenging. Here we present fC-CET, a bisulfite-free method for whole-genome analysis of 5fC based on selective chemical labeling of 5fC and subsequent C-to-T transition during PCR. Base-resolution 5fC maps showed limited overlap with 5hmC, with 5fC-marked regions more active than 5hmC-marked ones.

Trapping White Phosphorus within a Purely Organic Molecular Container Produced by Imine Condensation.

Three tetrahedral organic cages have been obtained by condensing a triamino linker with a set of three ostensibly analogous triformyl precursors. Despite the large number of imine bonds formed, the corresponding cages were obtained in exceptionally high yields. Both theory and experimental results demonstrate that intramolecular CH⋅⋅⋅π interactions within all of the cage frameworks play an important role in abetting the condensations and contributing to the near-quantitative synthetic yields. The three cages of this study exhibit high thermodynamic and kinetic stability. A variety of small neutral guest molecules with complementary sizes and geometries may be used as templates in the cage forming reactions. Among the guests that may be used in this way is white phosphorus (P4 ), whose inherent reactivity towards oxygen is almost fully attenuated when bound within one of the cages.

Two-bit memory and quantized storage phenomenon in conventional MOS structures with double-stacked Pt-NCs in an HfAlO matrix.

A two-bit memory and quantized storage phenomenon are observed at room temperature for a device based on the traditional MOS structure with double-stacked Pt-nanocrystals (Pt-NCs). A 2.68 and 1.72 V flat band voltage shift (memory window) has been obtained when applying a ±7 V programming/erasing voltage to the structures with double-stacked Pt-NCs. The memory windows of 2.40 and 1.44 V can be retained after stress for 10(5) seconds, which correspond to 89.55% and 83.72% stored charges reserved. The quantized charge storage phenomenon characterized by current-voltage (J-V) hysteresis curves was detected at room temperature. The shrinkage of the memory window results from the decreasing tunneling probability, which strongly depends on the number of stacks. The traps, de-traps and quantum confinement effects of Pt-NCs may contribute to the improvement of dielectric characteristics and the two-bit memory behavior. The multi-bit memory and quantized storage behavior observed in the Pt-NCs stacks structure at room temperature might provide a feasible method for realizing the multi-bit storage in non-volatile flash memory devices.

Preparation of VC nanoliposomes by high pressure homogenization: Process optimization and evaluation of efficacy, transdermal absorption, and stability.

Vitamin C (VC) possesses antioxidant and whitening effects. However, its effectiveness is hindered by challenges such as instability, impaired solubility, and limited bioavailability hinder. In this study, VC was encapsulated in nanoliposomes by primary emulsification and high-pressure homogenization. The VC nanoliposomes were comprehensively characterized for their microscopic morphology, particle size, polydispersity index (PDI), and encapsulation efficiency (EE). Orthogonal experiments were designed to optimize the optimal preparation process, and the antioxidant activity, whitening efficacy, transdermal absorption, and stability of VC nanoliposomes were evaluated based on this optimized process. The findings demonstrated the high reproducibility of the optimal process, with particle size, PDI, and EE values of 113.502 ± 4.360 nm, 0.104 ± 0.010, and 56.09 ± 1.01 %, respectively. Differential scanning calorimetry analysis showed effective encapsulation of VC nanoliposomes with better thermal stability than aqueous VC solution. Besides, the VC nanoliposomes demonstrated excellent antioxidant and whitening effects in efficacy experiments, stronger skin permeability in transdermal experiments and fluorescence tracking. Furthermore, storage stability tests indicated that the VC in nanoliposomes remained relatively stable after 60 days of storage. These findings highlighted the potential use of VC nanoliposomes in a wide range of applications for the cosmetic market, especially in the development of ingredients for skin care products.

A natural biological adhesive from snail mucus for wound repair.

The discovery of natural adhesion phenomena and mechanisms has advanced the development of a new generation of tissue adhesives in recent decades. In this study, we develop a natural biological adhesive from snail mucus gel, which consists a network of positively charged protein and polyanionic glycosaminoglycan. The malleable bulk adhesive matrix can adhere to wet tissue through multiple interactions. The biomaterial exhibits excellent haemostatic activity, biocompatibility and biodegradability, and it is effective in accelerating the healing of full-thickness skin wounds in both normal and diabetic male rats. Further mechanistic study shows it effectively promotes the polarization of macrophages towards the anti-inflammatory phenotype, alleviates inflammation in chronic wounds, and significantly improves epithelial regeneration and angiogenesis. Its abundant heparin-like glycosaminoglycan component is the main active ingredient. These findings provide theoretical and material insights into bio-inspired tissue adhesives and bioengineered scaffold designs.

A novel copper-catalyzed reductive coupling of N-tosylhydrazones with H-phosphorus oxides.

We report here a novel C(sp(3))-P bonds formation via copper-catalyzed reductive coupling of N-tosylhydrazones with H-phosphorus oxides. A variety of aliphatic and aromatic substrates bearing electron-rich and electron-deficient substituents affords phosphine oxide derivatives with moderate to good yields. This work suggests a new transformation of aldehydes/ketones via N-tosylhydrazones to organophosphorus compounds.

N-Hydroxyphthalimide exhibits antitumor activity by suppressing mTOR signaling pathway in BT-20 and LoVo cells.

BACKGROUND: N-Hydroxyphthalimide (NHPI), an important chemical raw material, was found to have potent and selective anti-proliferative effect on human breast carcinoma BT-20 cells, human colon adenocarcinoma LoVo and HT-29 cells during our screening for anticancer compounds. The purpose of this study is to assess the antitumor efficacy of NHPI in vitro and in vivo and to explore the underlying antitumor mechanism. METHODS: Cell cytotoxicity of NHPI was evaluated using MTS assay and cell morphological analysis. After NHPI treatment, cell cycle, apoptosis and mitochondrial membrane potential were analyzed using flow cytometer. The subcellular localization of eukaryotic initiation factor 4E (eIF4E) was analyzed by immunofluorescence assay. The antitumor efficacy of NHPI in vivo was tested in BT-20 xenografts. The underlying antitumor mechanisms of NHPI in vitro and in vivo were investigated with western blot analysis in NHPI-treated cancer cells and tumor tissues. Statistical significance was determined using Student's t-test. RESULTS: In vitro, NHPI selectively inhibited the proliferation and induced G2/M phase arrest in BT-20 and LoVo cells, which was attributed to the inhibition of cyclin B1 and cdc2 expressions. Furthermore, NHPI induced apoptosis via mitochondrial pathway. Of note, NHPI effectively inhibited mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTOR complex 2 (mTORC2) signaling, and overcame the feedback activation of Akt and extracellular signal-regulated kinase (ERK) caused by mTORC1 inhibition in BT-20 and LoVo cells. In vivo, NHPI inhibited tumor growth and suppressed mTORC1 and mTORC2 signaling in BT-20 xenografts with no obvious toxicity. CONCLUSIONS: We found for the first time that NHPI displayed antitumor activity which is associated with the inhibition of mTOR signaling pathway. Our findings suggest that NHPI may be developed as a promising candidate for cancer therapeutics by targeting mTOR signaling pathway and as such warrants further exploration.

Copper-mediated dimerization to access 3a,3a'-bispyrrolidinoindoline: diastereoselective synthesis of (+)-WIN 64821 and (-)-ditryptophenaline.

A copper-mediated cyclization and dimerization of tryptamine or tryptophan was developed to generate a C2-symmetry C3(sp(3))-C3(sp(3)) bridge with two contiguous stereogenic quaternary carbons in one step. Impressively, the ratio between exo and endo cyclization products varies when different protecting groups of Nb are utilized. This dimerization reaction could be conducted in gram scale. With this dimerization method, both endocyclotryptophan (+)-WIN 64821 and exocyclotryptophan (-)-ditryptophenaline were synthesized in 5 steps.