Synthesis of indoles via alkylidenation of acyl hydrazides

Indoles have been synthesised via alkylidenation of acyl phenylhydrazides using phosphoranes and the Petasis reagent, followed by in situ thermal rearrangement of the product enehydrazines. The Petasis reagent provides an essentially neutral equivalent of the [acid-catalysed] Fischer indole synthesis, but with acyl phenylhydrazides as starting substrates. Alkylidene triphenylphosphoranes convert aroyl phenylhydrazides to indoles, but acyl phenylhydrazides derived from aliphatic carboxylic acids undergo a Brunner reaction to form indolin-2-ones

High throughput synthesis of 2,5-substituted indoles using a titanium carbenoid bearing boronate functionality

A titanium benzylidene complex bearing a boronate group converted resin-bound esters into enol ethers. Suzuki cross-coupling with aryl iodides followed by cleavage with acid completed the solid-phase synthesis of 2,5-disubstituted N-Boc-indoles. Also reported is the use of tert-butyllithium and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane to convert an aryl bromide into an arylboronate in the presence of a dithiane, with simultaneous reduction of an aryl azide to an amine

Polar Diels-Alder Reactions using Heterocycles as Electrophiles. Influence of Microwave Irradiation

In this work we studied a series of polar Diels-Alder reactions using different heterocycles derivatives acting as electrophiles joint to dienes of different nucleophilicity, analyzing the effect of the microwave irradiation in these processes. We employ the technique in two conditions: benzene as solvent and solvent free reactions. The last one presents the better yield in shorter time of reaction. Using microwave heating the aromatic cycloadducts are clearly predominant. It is possible to demonstrate that the microwave irradiation has a better influence on these cycloaddition reactions respect to those developed in thermal classical conditions.Fil: Kneeteman, Maria Nelida. Universidad Nacional del Litoral. Facultad de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: López Baena, Anna Francesca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Ingeniería Química; ArgentinaFil: Della Rosa, Claudia Daniela. Universidad Nacional del Litoral. Facultad de Ingeniería Química; ArgentinaFil: Mancini, Pedro Maximo Emilio. Universidad Nacional del Litoral. Facultad de Ingeniería Química; Argentin

HBF4 Catalysed Nucleophilic Substitutions of Propargylic Alcohols

The activity of HBF4 (aqueous solution) as a catalyst in propargylation reactions is presented. Diverse types of nucleophiles were employed in order to form new C–O, C–N and C–C bonds in technical acetone and in air. Good to excellent yields and good chemoselectivities were obtained using low acid loading (typically 1 mol-%) under simple reaction conditions

Heterocyclic scaffolds as promising anticancer agents against tumours of the central nervous system: Exploring the scope of indole and carbazole derivatives

Tumours of the central nervous system are intrinsically more dangerous than tumours at other sites, and in particular, brain tumours are responsible for 3% of cancer deaths in the UK. Despite this, research into new therapies only receives 1% of national cancer research spend. The most common chemotherapies are temozolomide, procarbazine, carmustine, lomustine and vincristine, but because of the rapid development of chemoresistance, these drugs alone simply aren’t sufficient for long-term treatment. Such poor prognosis of brain tumour patients prompted us to research new treatments for malignant glioma, and in doing so, it became apparent that aromatic heterocycles play an important part, especially the indole, carbazole and indolocarbazole scaffolds. This review highlights compounds in development for the treatment of tumours of the central nervous system which are structurally based on the indole, carbazole and indolocarbazole scaffolds, under the expectation that it will highlight new avenues for research for the development of new compounds to treat these devastating neoplasms

Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation.

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting side effect of cancer treatment that affects millions of cancer survivors throughout the world and current treatment options are extremely limited by their side effects. Cannabinoids are highly effective in suppressing pain symptoms of chemotherapy-induced and other peripheral neuropathies but their widespread use is limited by central nervous system (CNS)-mediated side effects. Here, we tested one compound from a series of recently developed synthetic peripherally restricted cannabinoids (PRCBs) in a rat model of cisplatin-induced peripheral neuropathy. Results show that local or systemic administration of 4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3-yl]ethyl}morpholine (PrNMI) dose-dependently suppressed CIPN mechanical and cold allodynia. Orally administered PrNMI also dose-dependently suppressed CIPN allodynia symptoms in both male and female rats without any CNS side effects. Co-administration with selective cannabinoid receptor subtype blockers revealed that PrNMI's anti-allodynic effects are mediated by CB1 receptor (CB1R) activation. Expression of CB2Rs was reduced in dorsal root ganglia from CIPN rats, whereas expression of CB1Rs and various endocannabinoid synthesizing and metabolizing enzymes was unaffected. Daily PrNMI treatment of CIPN rats for two weeks showed a lack of appreciable tolerance to PrNMI's anti-allodynic effects. In an operant task which reflects cerebral processing of pain, PrNMI also dose-dependently suppressed CIPN pain behaviors. Our results demonstrate that PRCBs exemplified by PrNMI may represent a viable option for the treatment of CIPN pain symptoms

Chiral transition-metal complexes as Brønsted-acid catalysts for the asymmetric Friedel-Crafts hydroxyalkylation of indoles.

The Friedel-Crafts reaction between 3,3,3-trifluoropyruvates and indoles is efficiently catalysed by the iridium complex [(η5-C 5Me5)Ir{(R)-Prophos}(H2O)][SbF 6]2 (1) with up to 84% ee. Experimental data and theoretical calculations support a mechanism involving the Brønsted-acid activation of the pyruvate carbonyl by the protons of the coordinated water molecule in 1. Water is not dissociated during the process and, therefore, the catalytic reaction occurs with no direct interaction between the substrates and the metal. This journal is © the Partner Organisations 2014.The authors acknowledge the Ministerio de Economía y Competitividad (MINECO, Grants CTQ2006-03030/BQU, CTQ2009-10303/BQU, CTQ2011-27033 and Consolider Ingenio 2010 CSD2006-003), Gobierno de Aragón (Grupo Consolidado: Catálisis Homogénea Enantioselectiva), Generalitat de Catalunya (2009SGR0259) and the ICIQ foundation for financial support. A. S. and R. R. acknowledge MINECO for predoctoral fellowships. S. D.-G. acknowledges MINECO for a “Torres Quevedo” contract.Peer Reviewe