Unlocking regioselective meta-alkylation with epoxides and oxetanes via dynamic kinetic catalyst control.

Regioselective arene C-H bond alkylation is a powerful tool in synthetic chemistry, yet subject to many challenges. Herein, we report the meta-C-H bond alkylation of aromatics bearing N-directing groups using (hetero)aromatic epoxides as alkylating agents. This method results in complete regioselectivity on both the arene as well as the epoxide coupling partners, cleaving exclusively the benzylic C-O bond. Oxetanes, which are normally unreactive, also participate as alkylating reagents under the reaction conditions. Our mechanistic studies reveal an unexpected reversible epoxide ring opening process undergoing catalyst-controlled regioselection, as key for the observed high regioselectivities.

A controllable gelatin-based microcarriers fabrication system for the whole procedures of MSCs amplification and tissue engineering.

Biopolymer microbeads present substantial benefits for cell expansion, tissue engineering, and drug release applications. However, a fabrication system capable of producing homogeneous microspheres with high precision and controllability for cell proliferation, passaging, harvesting and downstream application is limited. Therefore, we developed a co-flow microfluidics-based system for the generation of uniform and size-controllable gelatin-based microcarriers (GMs) for mesenchymal stromal cells (MSCs) expansion and tissue engineering. Our evaluation of GMs revealed superior homogeneity and efficiency of cellular attachment, expansion and harvest, and MSCs expanded on GMs exhibited high viability while retaining differentiation multipotency. Optimization of passaging and harvesting protocols was achieved through the addition of blank GMs and treatment with collagenase, respectively. Furthermore, we demonstrated that MSC-loaded GMs were printable and could serve as building blocks for tissue regeneration scaffolds. These results suggested that our platform held promise for the fabrication of uniform GMs with downstream application of MSC culture, expansion and tissue engineering.

Effects of ECM proteins (laminin, fibronectin, and type IV collagen) on the biological behavior of Schwann cells and their roles in the process of remyelination after peripheral nerve injury.

Introduction: It is important to note that complete myelination and formation of myelinated fibers are essential for functional nerve regeneration after peripheral nerve injury (PNI). However, suboptimal myelin regeneration is common and can hinder ideal nerve regeneration. Therefore, it is important to closely monitor and support myelin regeneration in patients with PNI to achieve optimal outcomes. Methods: This study analyzed the effects of three extracellular matrix (ECM) proteins on Schwann cells (SCs) in the nerve regeneration environment, including their adhesion, proliferation, and migration. The study also explored the use of composite sodium alginate hydrogel neural scaffolds with ECM components and investigated the effects of ECM proteins on remyelination following peripheral nerve injury. Results: The results showed that laminin (LN), fibronectin (FN), and collagen Ⅳ (type IV Col) promoted the early adhesion of SCs in 2-dimensional culture but the ratios of early cell adhesion were quite different and the maintenance of cells' morphology by different ECM proteins were significantly different. In transwell experiment, the ability of LN and FN to induce the migration of SCs was obviously higher than that of type IV Col. An vitro co-culture model of SCs and dorsal root ganglia (DRG) neurons showed that LN promoted the transition of SCs to a myelinated state and the maturation of the myelin sheath, and increased the thickness of neurofilaments. Animal experiments showed that LN had superior effects in promoting myelin sheath formation, axon repair, and reaching an ideal G-ratio after injury compared to FN and Col IV. The situation of gastrocnemius atrophy was significantly better in the LN group. Notably, the thickness of the regenerated myelin sheaths in the type IV Col group was the thickest. Conclusion: In this experiment, we analyzed and compared the effects of LN, FN, and type IV Col on the biological behavior of SCs and their effects on remyelination after PNI and further clarified their unique roles in the process of remyelination. Further research is necessary to explore the underlying mechanisms.

Nickel-Catalyzed Sodium Hypophosphite-Participated Direct Hydrophosphonylation of Alkyne toward H-Phosphinates.

The traditional methods for the synthesis of phosphinate esters use phosphorus trichloride (PCl3) as the phosphorous source, resulting in procedures that are often highly polluting and energy intensive. The search for an alternative approach that is both mild and environmentally friendly is a challenging, yet highly rewarding task in modern chemistry. Herein, we use an inorganic phosphorous-containing species, NaH2PO2, to serve as the source of phosphorous that participates directly in the nickel-catalyzed selective alkyne hydrophosphonylation reaction. The transformation was achieved in a multicomponent fashion and at room temperature, and most importantly, the H-phosphinate product generated is an advanced intermediate which can be readily converted into diverse phosphinate derivatives, including those bearing new P-C, P-S, P-N, P-Se, and P-O bonds, thus providing a complimentary method to classic phosphinate ester synthesis techniques.

Carbonylative C-C Bond Activation of Aminocyclopropanes Using a Temporary Directing Group Strategy.

Temporary directing groups (TDGs) underpin a range of C-C bond activation methodologies; however, the use of TDGs for the regiocontrolled activation of cyclopropane C-C bonds is underdeveloped. In this report, we show how an unusual ring contraction process can be harnessed for TDG-based carbonylative C-C bond activations of cyclopropanes. The method involves the transient installation of an isocyanate-derived TDG, rather than relying on carbonyl condensation events as used in previous TDG-enabled C-C bond activations.

Rhodacyclopentanones as Linchpins for the Atom Economical Assembly of Diverse Polyheterocycles.

We outline a conceptual blueprint that provides direct and atom economical access to a wide range of complex polyheterocycles. Our method capitalizes on the ambiphilic reactivity of rhodacyclopentanones that arise upon exposure of cyclopropanes to Rh(I) catalysts and CO. Using this approach, a wide array of polycyclizations are achieved, including variants that involve powerful dearomatizations and medium ring formations.

Circular RNA expression pattern in cisplatin-resistant osteosarcoma cells.

BACKGROUND: Cisplatin resistance associated with circular RNA (circRNA) in osteosarcoma (OS) is not fully understood. The present study aimed to reveal the expression profile of circRNAs related to cisplatin resistance in OS. METHODS: Cisplatin-resistant OS cell lines (U2OS-R and MG63-R) were induced using different concentrations of cisplatin and RNA sequencing (RNA-seq) was performed to screen differentially expressed circRNAs in these cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the function of the differentially expressed circRNAs. The circRNAs identified by RNA-seq were randomly selected for expression identification by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: A total of 343 circRNAs were differentially expressed in U2OS-R cells compared with U2OS cells. Among these circRNAs, 253 were upregulated and 90 were downregulated. Analysis of the characteristics of the differentially expressed circRNAs showed that upregulated circRNAs were mainly distributed in chromosomes 1, 2, 3, 7, and 8, while downregulated circRNAs were distributed in all chromosomes except the X chromosome. GO and KEGG analyses revealed that the differentially expressed circRNAs were enriched in metabolic pathways, pathways in cancer, adherens junction, proteoglycans in cancer, and transcriptional misregulation in cancer pathway. Furthermore, three circRNAs (hsa_circ_0008336, hsa_circ_0004664, and hsa_circ_0003302) were upregulated in both U2OS-R and MG63-R cells. CONCLUSIONS: Cisplatin-resistant cell lines showed a distinct circRNA expression profile. In particular, hsa_circ_0008336, hsa_circ_0004664, and hsa_circ_0003302 were upregulated in cisplatin-resistant cells and may be involved in the pathology of cisplatin resistance in OS.

Modular Access to Eight-Membered N-Heterocycles by Directed Carbonylative C-C Bond Activation of Aminocyclopropanes.

Aminocyclopropanes equipped with pendant nucleophiles undergo carbonylative heterocyclization triggered by C-C bond activation to generate eight-membered N-heterocycles. In these processes, intramolecular "capture" of a rhodacyclopentanone intermediate by an aryl or N-based nucleophile is followed by C-C or C-N bond-forming "collapse" to the targets. These studies demonstrate how the combination of cyclopropane strain release and the templating effect of catalytically generated metallacycles can be harnessed to enable otherwise challenging medium ring closures.

Modular Access to Azepines by Directed Carbonylative C-C Bond Activation of Aminocyclopropanes.

A modular Rh-catalyzed entry to azepines is outlined. Under a CO atmosphere, protecting group directed C-C bond activation of aminocyclopropanes provides rhodacyclopentanones. These intermediates are effective for intramolecular C-H metalation of either an N-aryl or N-vinyl unit en route to azepine ring systems. Thus, byproduct-free heterocyclizations are enabled by sequential C-C activation and C-H functionalization steps.

New Initiation Modes for Directed Carbonylative C-C Bond Activation: Rhodium-Catalyzed (3 + 1 + 2) Cycloadditions of Aminomethylcyclopropanes.

Under carbonylative conditions, neutral Rh(I)-systems modified with weak donor ligands (AsPh3 or 1,4-oxathiane) undergo N-Cbz, N-benzoyl, or N-Ts directed insertion into the proximal C-C bond of aminomethylcyclopropanes to generate rhodacyclopentanone intermediates. These are trapped by N-tethered alkenes to provide complex perhydroisoindoles.

[Clinical research of needle-pricking therapy for functional retrograde ejaculatioin].

OBJECTIVE: To observe the clinical effects of needle-pricking therapy, a newly medical and minimally invasive technique, for functional retrograde ejaculation and to explore its mechanism. Methods Thirty-six patients with functional retrograde ejaculation were randomly divided into an observation group(19 cases) and a control group(17 cases) In the observation group,needle-pricking therapy was used at Guanyuan(CV 4) and bilateral sacral plexus nerve,lumbar 1 nerve and greater occipital nerve stimulating points,once a week. In the control group, midodrine tablets were prescribed orally,three times a day. All the treatment was given for 9 weeks. The clinical effects of the two groups were observed, and the levels of luteinizing hormone(LH), testosterone(Tes) and estra4 diol(E2) were compared between the two groups. RESULTS: The total effective rate of the observation group was, 89. 47%(17/19), which was better than 47.06% (8/17) of the control group(P<0. 05). The LH and Tes were obviously increased and E2 was decreased compared with those before treatment in the observation group(all P< 0. 01). Tes was raised(P<0. 05) and E2 was apparently declined in the control group(P<0. 01). After treatment, the differences of serum LH and Tes were statistically significant between the two groups(both P<0. 01). CONCLUSION: Needle-pricking therapy has advantages for functional retrograde ejaculation probably in that stimulating lumbosacral nerves can strengthen the function of pelvic floor muscles and urethral expansion muscle and regulate sexual gland axis.

Cu-Catalyzed selective cascade sp(3) C-H bond oxidative functionalization towards isoxazoline derivatives.

The first Cu-catalyzed cascade sp(3) C-H bond oxidative functionalization of the 2-ethylazaarenes has been developed. The two different sp(3) C-H bonds in 2-ethylazaarenes are selectively oxidized and four new types of bonds (C=O, C=N, C-C, C-O) are constructed in one operation. Starting from the simple substrates and cheap nitro source, this reaction provides an efficient approach to produce new kinds of isoxazolines.

Enantioselective synthesis of arylglycine derivatives by direct C-H oxidative cross-coupling.

A new method for the synthesis of chiral α-amino acid derivatives by enantioselective C-H arylation of N-aryl glycine esters with aryl boric acids in the presence of a chiral Pd(II)-catalyst has been developed. This work successfully integrates the direct C-H oxidation with asymmetric arylation and exhibits excellent enantioselectivity.

A unique copper-catalyzed cross-coupling reaction by hydrogen (H2) removal for the stereoselective synthesis of 3-phosphoindoles.

The first Cu(i)-catalyzed cross-coupling reaction by hydrogen (H2) removal for the stereoselective synthesis of 3-phosphoindoles is reported. Going beyond the oxidative dehydrogenative coupling reactions reported recently, this reaction completely omits the oxidant and base, producing hydrogen (H2) as the only byproduct.

Regio- and stereoselective allylic C-H arylation with electron-deficient arenes by 1,1'-bi-2-naphthol-palladium cooperation.

A palladium-catalyzed allylic C-H arylation reaction with electron-deficient arenes with high regio- and stereoselectivity is reported. This work represents the first successful use of 1,1'-bi-2-naphthol as the ancillary ligand in allylic C-H activation, which is the key factor for chemoselectivity. Furthermore, high selectivity allylic C-H acetoxylation and amination were also successfully achieved under the same catalytic system.

Pd(II)-catalyzed C(sp2)-H hydroxylation with R2(O)P-coordinating group.

A novel R2(O)P-directed Pd(II)-catalyzed C-H hydroxylation to synthesize various substituted 2'-phosphorylbiphenyl-2-ol compounds is described. Notably, the reaction operates under mild conditions and shows good functional group tolerance, high selectivity, and yield.

Palladium-catalyzed sp2 and sp3 C-H bond activation and addition to isatin toward 3-hydroxy-2-oxindoles.

The first Pd(II)-catalyzed C-H addition to isatins by direct sp(2)/sp(3) C-H bond activation for the construction of 3-substituted-3-hydroxy-2-oxindoles is reported. The bidentate nitrogen ligands were found to promote this reaction. Specifically, the preliminary bioassay indicated that 3-(5-chlorobenzoxazole)-3-hydroxy-N-benzyl-2-oxindole (2w) is a new inhibitor of human kidney cancer and hepatocellular carcinoma cells. Moreover, this reaction system exhibits great functional group tolerance and requires no directing group, extra base, or additives.

Silver catalyzed intramolecular cyclization for synthesis of 3-alkylideneoxindoles via C-H functionalization.

A novel protocol for the preparation of various 3-alkylideneoxindoles via a silver-catalyzed aromatic C-H functionalization has been developed. The process is simple, environmentally conscious, and avoids the use of abundant bases, oxidants, or other additives.

Unexpected domino reaction via Pd-catalyzed Sonogashira coupling of benzimidoyl chlorides with 1,6-enynes and cyclization to synthesize quinoline derivatives.

A domino reaction via palladium-catalyzed Sonogashira coupling of benzimidoyl chlorides with 1,6-enynes and then cyclization to form quinoline derivatives has been developed. The reaction conditions and the scope of the process are examined, and a plausible mechanism is proposed. The procedure is simple, rapid, and general, and the substrates are readily available.