Synthesis and Biological Evaluation of 3-cyano-4H-chromene Derivatives Bearing Carbamate Functionality.

Background: 2-Aminochromene derivatives display important pharmacological properties, including mainly antibiotic and anticancer activities.

Objective: The study aims to synthesize new chromene derivatives via a new approach using Grignard reagents, for the evaluation of their antibiotic and antifungal properties.

Method: A series of novel 3-cyano-4-aminochromene derivatives bearing alkyl substituents at the 4-position was prepared for biological evaluation.

Successive addition of two different Grignard reagents to nitriles: access to α,α-disubstituted propargylamine derivatives.

The successive addition of two different Grignard reagents to acyl cyanohydrins was performed with success by taking advantage of the low reactivity of alkynyl Grignard reagents. The experimental conditions were adjusted so that they were not reactive during the first addition step, but reactive only in the second one. The synthetic utility of the prepared compounds was validated by the preparation of chiral quaternary α-amino acids.

Cyclopropyl-tryptamine analogues: synthesis and biological evaluation as 5-HT(6) receptor ligands.

Conformational restrictions: Based on the pharmacophore model for 5-HT(6) receptor ligands (shown), tryptamine analogues bearing a cyclopropyl ring on the α-position of the tryptamine side chain were synthesized and evaluated against 5-HT receptors. N,N-Dimethyl-1-arylsulfonyltryptamine derivatives exhibited promising selectivity for 5-HT(6) over 5-HT(1a) and 5-HT(4) receptors and interesting activity against 5-HT(6) (K(i) =∼0.15 μM; IC(50) =∼0.

Simple and convenient access to α,α,α-trisubstituted amides by double addition of Grignard reagents to acyl cyanohydrins.

The double addition of Grignard (alkyl, aryl, alkenyl, alkynyl) reagents to acyl cyanohydrins was performed under unusually smooth conditions with a concomitant O-N acyl transfer, providing a very simple and general access to α,α,α-trisubstituted amides.

The spirocyclopropyl moiety as a methyl surrogate in the structure of l-fucosidase and l-rhamnosidase inhibitors.

Nitrogen-in-the-ring analogues of l-fucose and l-rhamnose were prepared, which feature a spirocyclopropyl moiety in place of the methyl group of the natural sugar. The synthetic route involved a titanium-mediated aminocyclopropanation of a glycononitrile as the key step. Four new spirocyclopropyl iminosugar analogues were generated, which displayed some activity towards l-fucosidase and l-rhamnosidase.

Solvent-free direct reductive amination by catalytic use of an organotin reagent incorporated on an ionic liquid.

An organotin reagent supported on an ionic liquid was used as a highly effective catalyst (down to 0.1 mol%) for the direct reductive amination of aldehydes and ketones using PhSiH3; this solvent-free method facilitates purification of the products, thus minimizing the contamination by tin.

Cyclopropenylcarbinol derivatives as new versatile intermediates in organic synthesis: application to the formation of enantiomerically pure alkylidenecyclopropane derivatives.

The copper-catalyzed carbomagnesiation (or hydrometalation) reaction of chiral cyclopropenylcarbinol derivatives, obtained by means of a kinetic resolution of secondary allylic alcohols, leads to an easy and straightforward preparation of enantiomerically pure alkylidenecyclopropane derivatives. The reaction mechanism is composed of a syn-carbometalation followed by a syn-elimination reaction. To gain further insight into the reaction mechanism of the carbometalation, the diastereoselective formation of cyclopropylcarbinol was also achieved and was found to be very sensitive to the nature of the organometallic species used for the addition reaction.

Synthesis of a C-glucosylated cyclopropylamide and evaluation as a glycogen phosphorylase inhibitor.

The synthesis of carbohydrate-based glycogen phosphorylase inhibitors is attractive for potential applications in the treatment of type 2 diabetes. A titanium-mediated synthesis led to a benzoylated C-glucosylated cyclopropylamine intermediate, which underwent a benzoyl migration to afford the corresponding 2-hydroxy-C-glycoside. X-ray crystallographic studies revealed a unit cell composed of four molecules as pairs of dimers connected through two hydrogen bonds.

Diene-titanium complexes as synthetic intermediates for the construction of three- or five-membered carbocycles.

It has been shown that diene-titanium complexes exhibit substrate-dependent 1,2- or 1,4-dicarbanion reactivity. On this basis, 3-cyclopentenylamines and spiro-vinylcyclopropane lactams were easily prepared by using homoallylic Grignard reagents, Ti(O-i-Pr)4, and nitriles or cyanoesters, respectively.

Titanium- and Lewis acid-mediated cyclopropanation of imides.

We report a straightforward synthesis of 1-azaspirocyclopropane lactams from imides. Following the described procedure, polycyclic nitrogen heterocycles containing a cyclopropane unit could be obtained from unsaturated imides. [reaction: see text].

Spirocyclopropyl pyrrolidines as a new series of alpha-L-fucosidase inhibitors.

Polyhydroxy 4-azaspiro[2.4]heptane derivatives (spirocyclopropyl iminosugars) were prepared in four to six steps from readily available protected aldoses. The key step of the reaction sequence involves a titanium-mediated aminocyclopropanation of glycononitriles with subsequent cyclization.

Titanium-mediated [4 + 1] assembly of 1,3-dienes and nitriles: formation of 3-cyclopentenyl amines and cyclopentenones.

In the presence of Ti(OiPr)4 and iPrMgCl, dienes couple with nitriles to afford the title products in good yields.

A direct synthesis of 1-aryl- and 1-alkenylcyclopropylamines from aryl and alkenyl nitriles.

The reaction of various aromatic nitriles with 1.1 equiv of Ti(Oi-Pr)(4) and 2.2 equiv of EtMgBr followed by addition of a Lewis acid gave 1-aryl cyclopropylamines in 43-76% yields.

New and easy route to primary cyclopropylamines from nitriles.

Starting from readily available substrates, we have developed a new synthesis of primary cyclopropylamines. The reaction involves a cooperative Ti(II)- and Lewis acid-mediated coupling of alkanenitriles with Grignard reagents.

Ti(II)-mediated conversion of alpha-heterosubstituted (O, N, S) nitriles to functionalized cyclopropylamines. Effect of chelation on the cyclopropanation step.

Alpha-alkoxy, amino-, and thio nitriles undergo a Ti(II)-mediated coupling with Grignard reagents to afford heterofunctionalized cyclopropylamines. A chelation effect appears to be generally responsible for the spontaneous contraction of the intermediate azatitanacycle leading to cyclopropane. By using the described reaction, 1-aminocyclopropanecarboxylic acids were prepared in four steps, in good overall yields, from the readily available benzyloxyacetonitrile.

First evidence for the use of organosilver compounds in Pd-catalyzed coupling reactions; a mechanistic rationale for the Pd/Ag-catalyzed enyne synthesis?

Silver acetylides have been prepared and used in Pd-catalyzed coupling reactions. Enynes have thus been obtained in good yields. This work demonstrates that organosilver compounds could enter the Pd catalytic cycle; it also supports the role of silver acetylides as intermediates in the new Pd/Ag-catalyzed coupling reaction.

Multiple pulmonary chondromata. A rare cause of neonatal respiratory distress.

A neonate with respiratory distress due to a right pneumothorax is presented. After drainage of the pneumothorax, atelectasis of the entire right lung developed. Because the atelectasis persisted, bronchoscopy was performed.

Theory and practice: bridging scientists' and practitioners' roles.

Past and recent progress in theory development for psychiatric mental health nursing (PMHN) and its link to practice are reviewed. Results of a national survey of practitioners reflecting the current use of theory from the disciplines of nursing, psychiatry, and behavioral sciences are reported. Progress addressed in furthering the science of PMHN includes the taxonomy of nursing diagnoses and concept analysis.