Stereoselective Multicomponent Assembly of Enantiopure Oxazolopiperidines and -azepines

A multicomponent reaction (MCR) based on a cyclohydrocarbonylation (CHC) driven by hydroformylation was set up toward the efficient diastereoselective preparation of oxazolopiperidines (<b>4a</b>–<b>e</b>) and -azepines (<b>7a</b>–<b>d</b>). The bicyclic oxazolidines were obtained from chiral <i>N</i>-alkenylamino alcohols via transient cyclic iminium intermediates that underwent an intramolecular cyclization from the appendant oxygen. On the basis of a series of different experimental conditions, the diastereocontrol observed during the formation of the oxazolidines is best explained by the stereoelectronic effect induced by an A^1,3-strain in a common cyclic iminium intermediate (<b>A</b>). This new sequence is suitable for diversity oriented syntheses, allowing the preparation of enantiopure (<i>S</i>)- and (<i>R</i>)-coniceine in five steps from commercially available material

From Alcohols to Indoles: A Tandem Ru Catalyzed Hydrogen-Transfer Fischer Indole Synthesis

In a new version of the Fischer indole synthesis, primary and secondary alcohols have been catalytically oxidized in the presence of phenylhydrazines and protic or Lewis acids to give the corresponding indoles. The overall reaction can be accomplished in one step, and the use of alcohols instead of aldehyes or ketones as starting materials has several advantages in terms of a large selection of reagents, easy handling, and safety of the process

Domino Hydrogenation–Reductive Amination of Phenols, a Simple Process To Access Substituted Cyclohexylamines

Phenols can be efficiently reduced by sodium formate and Pd/C as the catalyst in water and in the presence of amines to give the corresponding cyclohexylamines. This reaction works at rt for 12 h or at 60 °C under microwave dielectric heating for 20 min. With the exception of aniline, primary, secondary amines, amino alcohols, and even amino acids can be used as nucleophiles. The reductive process is based on a sustainable hydrogen source and a catalyst that can be efficiently recovered and reused. The protocol was developed into a continuous-flow production of cyclohexylamines in gram scale achieving very efficient preliminary results (TON 32.7 and TOF 5.45 h^–1)

Synthesis of α,β-Unsaturated Aldehydes Based on a One-Pot Phase-Switch Dehydrogenative Cross-Coupling of Primary Alcohols

An efficient <i>one-pot</i> ruthenium-catalyzed hydrogen-transfer strategy for a direct access to α,β-unsaturated aldehydes has been developed. The employment of enolates prepared in situ from alcohols avoided handling unstable aldehydes and provided a very appealing route to different cinnamaldehydes substituted in position 2. A silica-grafted amine was used as phase-switch tag leading to a selective one-pot process in favor of cross-dehydrogenative coupling products

SMO RNA expression in KU-812 cells.

<p>Effects of compounds MRTX, MRT94, MRT92, MRT83, MRTY and control compound in KU-812 cells on SMO RNA expression after 24h (a) or 72h (b) treatment at 10 μM and treatment after 24h (c) or 72h (d) at 50 μM. Data are expressed as the means ± SEM of three independent experiments performed in triplicate. *p<0.05 vs medium.</p

Pro-autophagic activity of the compounds expressed as BNIP3 RNA levels.

<p>Effects of compounds MRTX, MRT94, MRT92, MRT83, MRTY and control compound after a 72h treatment at 10 μM on BNIP3 RNA ratio in K-562 cells (a) and KU-812 cells (b). Data are expressed as the means ± SEM of three independent experiments performed in triplicate. *p<0.05 vs medium.</p

Effects of compounds and controls on Gli1 and SuFu protein expression.

<p>Effects of compounds MRT83, MRTX, MRT92, MRTY, MRT94 and control compounds after a 24 h treatment at 20 μM on Gli1 and SuFu protein expression in K-562 cells (a) and KU-812 cells (b) and quantification relative to medium expression (c-d). β-actin was used as loading control. Data are representative images, quantifications are expressed as the means ± SEM of three independent experiments. *p<0.05 vs medium.</p

Pro-apoptotic activity of the compounds expressed as ratio between Bax and Bcl-2 RNA levels.

<p>Effects of compounds MRTX, MRT94, MRT92, MRT83, MRTY and control compound after a 72h treatment at 10 μM on Bax/Bcl2 RNA ratio in K-562 cells (a) and KU-812 cells (b). Data are expressed as the means ± SEM of three independent experiments performed in triplicate. *p<0.05 vs medium.</p

Pro-apoptotic activity of the compounds on PARP cleavage.

<p>Effects of compounds MRTX, MRT94, MRT92, MRT83, MRTY and control compound after a 72h treatment at 10 μM on PARP cleavage in K-562 cells (a) and KU-812 cells (b). β-actin was used as loading control. Data are representative images of three independent experiments.</p

Antiproliferative effects of the new compounds toward K-562 and KU-812 cell lines.

<p>Antiproliferative effects of the new compounds toward K-562 and KU-812 cell lines.</p