Visible-light-induced photocatalytic four-component fluoroalkylation-dithiocarbamylation via difunctionalization of styrenes.

Herein we demonstrate that a visible-light-induced photocatalytic four-component fluoroalkylation-dithiocarbamylation is a unified method for the fluoroalkylation of diverse activated fluoroalkyl halides, including monofluoroalkyl bromides, difluoroalkyl bromides, trifluoromethyl iodide, and perfluoroalkyl iodides. The synthetic value of this method has been demonstrated by the transformations of various substrates containing drug/natural product skeletons, gram scale reactions, and further derivatizations of the fluorodithiocarbamate products. This work features an atom economical protocol that is simple to operate, does not require any additives or strong bases, and can be carried out under mild conditions.

Genipin Analogue (G300) Inhibits Adipogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells through the Suppression of Adipogenic Promoting Factors.

While obesity is a well-known health threatening condition worldwide, effective pharmacological interventions for obesity suppression have been limited due to adverse effects. Therefore, it is important to explore alternative medical treatments for combating obesity. Inhibition of the adipogenesis process and lipid accumulation are critical targets for controlling and treating obesity. Gardenia jasminoides Ellis is a traditional herbal remedy for various ailments. A natural product from its fruit, genipin, has major pharmacological properties; it is anti-inflammatory and antidiabetic. We investigated the effects of a genipin analogue, G300, on adipogenic differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs). G300 suppressed the expression of adipogenic marker genes and adipokines secreted by adipocytes at concentrations of 10 and 20 µM, which effectively reduced the adipogenic differentiation of hBM-MSCs and lipid accumulation in adipocytes. It also improved adipocyte function by lowering inflammatory cytokine secretion and increasing glucose uptake. For the first time, we show that G300 has the potential to be a novel therapeutic agent for the treatment of obesity and its related disorders.

Divergent Synthesis of 3-Pyrrolidin-2-yl-1H-indoles, Symmetric and Unsymmetric Bis(Indolyl)Methanes (BIMs) through Photocatalyzed Decarboxylative Coupling/Friedel-Crafts Alkylation Reaction.

This paper reports the acid-controlled divergent synthesis of 3-pyrrolidin-2-yl-1H-indoles and symmetric and unsymmetrical bis(indolyl)methanes (BIMs) through photocatalyzed decarboxylative coupling and Friedel-Crafts alkylation reactions, respectively. The protocol involves C-H functionalization, switching formation of two products, room-temperature conditions, low photocatalyst loadings, without strong oxidant, and moderate to excellent yields. This method has been applied for the synthesis of natural product vibrindole A and 1,1-bis(1H-indol-3-yl)-2-phenylethane.

New 1,2,3-Triazole-genipin Analogues and Their Anti-Alzheimer's Activity.

A novel series of 1,2,3-triazole-genipin analogues were designed, synthesized, and evaluated for neuroprotective activity, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) inhibitory activity. The genipin analogues bearing bromoethyl- and diphenylhydroxy-triazole showed in vitro neuroprotective properties against H2O2 toxicity along with potent inhibitory activity on BuChE with IC50 values of 31.77 and 54.33 µM, respectively, compared with galantamine (IC50 = 34.05 µM). The molecular docking studies of these genipin analogues showed good binding energy and interact well with the key amino acids of BuChE via hydrogen-bonding and hydrophobic interactions. Triazole genipins might be promising lead compounds as anti-Alzheimer's agents.

Synthesis of propargylamine mycophenolate analogues and their selective cytotoxic activity towards neuroblastoma SH-SY5Y cell line.

Twenty six propargylamine mycophenolate analogues were designed and synthesized from mycophenolic acid 1 employing a key step A3-coupling reaction. Their cytotoxic activity was examined against six cancer cell lines. Compounds 6a, 6j, 6t, 6u, and 6z exhibited selective cytotoxicity towards neuroblastoma (SH-SY5Y) cancer cells and were less toxic to normal cells in comparison to the lead compound, MPA 1 and a standard drug, ellipticine. Molecular docking results suggested that compound 6a is fit well in the key amino acid of three proteins (CDK9, EGFR, and VEGFR-2) as targets in cancer therapy. The propargylamine mycophenolate scaffold might be a valuable starting point for development of new neuroblastoma anticancer drugs.

Hypervalent-Iodine(III)-Mediated Tandem Oxidative Dearomatization/Aziridination of Phenolic Amines: Synthesis of Functionalized Unactivated Aziridines.

A new hypervalent-iodine(III)-mediated tandem reaction involving oxidative dearomatization and in situ aziridination of phenolic amines is described, providing a mild and effective method for the assembly of structurally interesting and synthetically useful aziridines. Importantly, the densely functionalized aziridines resulting from this unprecedented tandem reaction offer a platform for expeditious access to architecturally diverse aza-heterocycles through transformations initiated by selective ring-opening of aziridines.

Synthetic analogues of durantoside I from Citharexylum spinosum L. and their cytotoxic activity.

New iridoid glycoside derivatives from durantoside I, the latter from the dried flowers and leaves of Citharexylum spinosum, were synthesized by variously modifying a sugar moiety by silylation or acetylation and/or removal of cinnamate group at C-7 position and subsequent screening for comparative cytotoxicity against several cancer cell lines. Addition of alkylsilane to durantoside I and removal of cinnamate group were most effective in improving cytotoxicity.