Activation of AKT-mTOR Signaling Directs Tenogenesis of Mesenchymal Stem Cells.

Tendon repair is a clinical challenge because of the limited understanding on tenogenesis. The synthesis of type I collagen (Collagen I) and other extracellular matrix are essential for tendon differentiation and homeostasis. Current studies on tenogenesis focused mostly on the tenogenic transcriptional factors while the signaling controlling tenogenesis on translational level remains largely unknown. Here, we showed that mechanistic target of rapamycin (mTOR) signaling was activated by protenogenic growth factor, transforming growth factors beta1, and insulin-like growth factor-I. The expression of mTOR was upregulated during tenogenesis of mesenchymal stem cells (MSCs). Moreover, mTOR was downregulated in human tendinopathy tissues and was inactivated upon statin treatment. Both inhibition and depletion of AKT or mTOR significantly reduced type I collagen production and impaired tenogenesis of MSCs. Tendon specific-ablation of mTOR resulted in tendon defect and reduction of Collagen I. However, there is no evident downregulation of tendon associated collagens at the transcription level. Our study demonstrated that AKT-mTOR axis is a key mediator of tendon differentiation and provided a novel therapeutic target for tendinopathy and tendon injuries. Stem Cells 2018;36:527-539.

Silver-Catalyzed Synthesis of Benzyl Ethers via Alkoxylation of Benzylic C(sp3 )-H Bonds.

Alkoxylation of benzylic C(sp3 )-H bonds has become one of the most important tools for the construction of benzyl ethers from feedstock chemicals. Herein, we reported a silver catalyzed alkoxylation of benzylic C(sp3 )-H bonds employing potassium persulfate as an oxidant at room temperature. This strategy showed good functional-group tolerance, site selectivity, and chemoselectivity. The reaction proceeded smoothly in the presence of various primary, secondary, and tertiary alcohol nucleophiles, affording corresponding benzyl ethers. Combined experimental studies provided mechanistic insights into the possible radical pathways. Furthermore, a possible mechanism was proposed for this method.

Copper-Catalyzed Asymmetric Cyanation of Propargylic Radicals via Direct Decarboxylation of Propargylic Carboxylic Acids.

Chiral propargylic cyanides are often used as small-molecule feedstocks for the introduction of chiral centers into various valuable products and complex molecules. Here, we have developed a highly atom-economical strategy for the chiral copper complex-catalyzed synthesis of chiral propargylic cyanides. Propargylic radicals can be smoothly obtained by direct decarboxylation of the propargylic carboxylic acids without preactivation. The reactions show excellent selectivity and functional group compatibility. Gram-scale reaction and several conversion reactions from chiral propargylic cyanide have demonstrated the synthetic value of this strategy.

Dual Photoredox/Nickel-Catalyzed Dehydrative Difluoroalkylation of Benzyl Alcohols for the Synthesis of Allylic gem-Difluorides.

A photoredox/Lewis acid cooperative catalytic system has been developed for the construction of Cvinyl-CRf bonds through the dehydrative difluoroalkylation of benzyl alcohols. A variety of allylic gem-difluorides could be obtained in moderate yields with good to excellent E/Z selectivity. In addition, several control experiments have been explored, and a possible mechanism was proposed for this process.

Copper-Catalyzed Enantioselective Decarboxylative Cyanation of Benzylic Acids Promoted by Hypervalent Iodine(III) Reagents.

Copper-catalyzed asymmetric radical cyanation reactions have emerged as a powerful strategy for rapid construction of α-chiral nitriles. However, the directly decarboxylative cyanation reactions of common alkyl carboxylic acids remain largely elusive. Herein, we report a protocol for copper-catalyzed direct and enantioselective decarboxylative cyanation of benzylic acids. The in situ activation of acid substrates by a commercially inexpensive hypervalent iodine(III) reagent promoted the yield of the alkyl radicals under mild reaction conditions without prefunctionalization. The structurally diverse chiral alkyl nitriles were produced in good yields with high enantioselectivities. In addition, the chiral products can be readily converted to other useful chiral compounds via further transformations.

Cu-Catalyzed Dehydrogenative Olefinsulfonation of Alkyl Arenes.

A copper-catalyzed reaction protocol for the dehydrogenation of ethylbenzenes into styrene derivatives has been developed. This reaction procedure proceeded well under mild reaction conditions, providing a practical and efficient strategy for the rapid assembly of biologically and pharmaceutically significant molecules, such as vinyl sulfone. Simple alkyl arenes were functionalized via consecutive ß-elimination in the presence of N-sulfonylbenzo[d]imidazole with broad substrate scope and good functional group tolerance.