An Annulative Synthetic Strategy for Building Triphenylene Frameworks by Multiple C-H Bond Activations.

C-H activation is a versatile tool for appending aryl groups to aromatic systems. However, heavy demands on multiple catalytic cycle operations and site-selectivity have limited its use for graphene segment synthesis. A Pd-catal- yzed one-step synthesis of functionalized triphenylene frameworks is disclosed, which proceeds by 2- or 4-fold C-H arylation of unactivated benzene derivatives. A Pd2 (dibenzylideneacetone)3 catalytic system, using cyclic diaryliodonium salts as π-extending agents, leads to site-selective inter- and intramolecular tandem arylation sequences. Moreover, N-substituted triphenylenes are applied to a field-effect transistor sensor for rapid, sensitive, and reversible alcohol vapor detection.

A palladium and gold catalytic system enables direct access to O- and S-linked non-natural glyco-conjugates.

Here we report a straightforward cross-coupling method for the synthesis of non-natural glycoamino acids from alkyne-bearing monosaccharides and p-iodophenylalanine. Pd/Au-catalyzed Sonogashira coupling is tolerant to both O- and S-glycosides without any epimerization. In addition, no racemization of the amino acid was observed allowing direct access to the homogeneous glyco-conjugate in a single step. Notably, this Pd/Au catalytic system presents enhanced catalytic activity than conventional Pd/Cu and Pd-only platforms, and it further enables the convergent synthesis of glycodipeptides.

A Novel Chemotherapeutic Agent to Treat Tumors with DNA Mismatch Repair Deficiencies.

Impairing the division of cancer cells with genotoxic small molecules has been a primary goal to develop chemotherapeutic agents. However, DNA mismatch repair (MMR)-deficient cancer cells are resistant to most conventional chemotherapeutic agents. Here we have identified baicalein as a small molecule that selectively kills MutSα-deficient cancer cells. Baicalein binds preferentially to mismatched DNA and induces a DNA damage response in a MMR-dependent manner. In MutSα-proficient cells, baicalein binds to MutSα to dissociate CHK2 from MutSα leading to S-phase arrest and cell survival. In contrast, continued replication in the presence of baicalein in MutSα-deficient cells results in a high number of DNA double-strand breaks and ultimately leads to apoptosis. Consistently, baicalein specifically shrinks MutSα-deficient xenograft tumors and inhibits the growth of AOM-DSS-induced colon tumors in colon-specific MSH2 knockout mice. Collectively, baicalein offers the potential of an improved treatment option for patients with tumors with a DNA MMR deficiency. Cancer Res; 76(14); 4183-91. ©2016 AACR.

An eco-friendly synthesis and antimicrobial activities of dihydro-2H-benzo- and naphtho-1,3-oxazine derivatives.

A series of 3,4-dihydro-2H-benzo[e]-, 2,3-dihydro-1H-naphtho[1,2-e]-, 3,4-dihydro-2H-naphtho[2,1-e][1,3]oxazine and 1,2-bis(3,4-dihydrobenzo[e][1,3]oxazin-3(4H)-yl)ethane derivatives was obtained through an eco-friendly Mannich type condensation-cyclization reaction of phenols or naphthols with formaldehyde and primary amines in water at ambient temperature. Preliminary in vitro antimicrobial activity of the synthesized compounds was assessed against six pathogenic fungi, two Gram-negative and two Gram-positive bacteria. Some of the screened compounds have shown significant in vitro antimicrobial effect. Cytotoxic activities of the lead compounds (2m, 2n, 3c and 3d) against mouse fibroblast cell line (L929) were determined by MTT method. The assay results revealed that these molecules offered remarkable viability (>90%) of L929 cells at concentration of 25 microg/mL.

Recent approaches to antifungal therapy for invasive mycoses.

Invasive fungal infections with primary and opportunistic mycoses have become increasingly common in recent years and pose a major diagnostic and therapeutic challenge. They represent a major area of concern in today's medical fraternity. The occurrence of invasive fungal diseases, particularly in AIDS and other immunocompromised patients, is life-threatening and increases the economic burden. Apart from the previously known polyenes and imidazole-based azoles, newly discovered triazoles and echinocandins are more effective in terms of specificity, yet some immunosuppressed hosts are difficult to treat. The main reasons for this include antifungal resistance, toxicity, lack of rapid and microbe-specific diagnoses, poor penetration of drugs into sanctuary sites, and lack of oral or intravenous preparations. In addition to combination antifungal therapy, other novel antimycotic treatments such as calcineurin signaling pathway blockers and vaccines have recently emerged. This review briefly summarizes recent developments in the pharmacotherapeutic treatment of invasive fungal infections.