A Thorough Study on the Photoisomerization of Ferulic Acid Derivatives

AbstractA thorough study on the (E) to (Z) photoisomerization of ferulic acid derivatives (esters, amides of all types, and ketones) was carried out. At the photostationary state, only aliphatic or benzylic tertiary amides reach a nearly complete conversion of (E) isomers into the (Z) ones, whereas for esters, primary and secondary amides or aromatic tertiary amides mixtures of (Z)/(E) ranging from 7 : 93 to 72 : 28 are observed. Ketones show rather limited photoisomerization. However, (Z) ketones may be obtained by the reaction of organometal compounds with an isomerized (Z) Weinreb amide

Multicomponent Synthesis of Polyphenols and Their In Vitro Evaluation as Potential \u3b2-Amyloid Aggregation Inhibitors

While plant polyphenols possess a variety of biological properties, exploration of chemical diversity around them is still problematic. Here, an example of application of the Ugi multicomponent reaction to the combinatorial assembly of artificial, yet \u201cnatural-like\u201d, polyphenols is presented. The synthesized compounds represent a second-generation library directed to the inhibition of \u3b2-amyloid protein aggregation. Chiral enantiopure compounds, and polyphenol-\u3b2-lactam hybrids have been prepared too. The biochemical assays have highlighted the importance of the key pharmacophores in these compounds. A lead for inhibition of aggregation of truncated protein A\u3b2pE3-42 was selected

Ketene 3\u2010Component Staudinger Reaction (K\u20103CSR) to \u3b2\u2010Lactams: A New Entry in the Class of Photoinduced Multicomponent Reactions

The Staudinger synthesis of \u3b2-lactams from imines and ketenes has been conducted photochemically only in very limited cases. Recent advances in the visible light mediated Wolff rearrangement of diazoketones allowed us to perform, for the first time, a 3-component Staudinger reaction, by mixing aldehydes, amines and diazoketones in the dark and switching the light on after imine formation. The new photoinduced reaction parallels the classic methods in terms of efficiency/selectivity and adds to the existing multicomponent approaches for the preparation of combinatorial libraries of compounds. A thorough optimization of the reaction conditions was performed both for the classic two component reaction and for the novel three component version of the photoinduced Staudinger reactio

Integrating biocatalysis and multicomponent reactions

While often multicomponent reactions (MCR) are used for the diversity-oriented synthesis of racemic (or achiral) molecular entities, this short review describes two alternative approaches for accessing enantiopure products exploiting the power of biocatalysis. Enzymes or microorganisms may be used for preparing enantiopure MCR inputs or for resolving racemic (or achiral) MCR adducts

Synthesis of seven-membered nitrogen heterocycles through the Ugi multicomponent reaction

This paper reviews all the syntheses of 7-membered nitrogen heterocycles that are based on the Ugi multicomponent reaction. Different systems may be obtained in a diversity-oriented manner employing three general strategies: i) intramolecular Ugi reaction; ii) Ugi reaction followed by cyclization involving one additional functional group; iii) Ugi reaction followed by cyclization involving two additional functional groups

In silico deconstruction of ATP-competitive inhibitors of glycogen synthase kinase-3\u3b2

Fragment-based methods have emerged in the last two decades as alternatives to traditional high throughput screenings for the identification of chemical starting points in drug discovery. One arguable yet popular assumption about fragment-based design is that the fragment binding mode remains conserved upon chemical expansion. For instance, the question of the binding conservation upon fragmentation of a molecule is still unclear. A number of papers have challenged this hypothesis by means of experimental techniques, with controversial results, "underlining" the idea that a simple generalization, maybe, is not possible. From a computational standpoint, the issue has been rarely addressed and mostly to test novel protocols on limited data sets. To fill this gap, we here report on a computational retrospective study concerned with the in silico deconstruction of leadlike compounds, active on the pharmaceutically relevant enzyme glycogen synthase kinase-3\u3b2. \ua9 2012 American Chemical Society

Synthesis of Polyoxygenated Heterocycles by Diastereoselective Functionalization of a Bio-Based Chiral Aldehyde Exploiting the Passerini Reaction

A chiral bio-based building block, prepared by the lipase-mediated desymmetrization of an erythritol derivative, was further functionalized and then submitted to stereoselective Passerini reactions, allowing the synthesis of a small library of new molecules. Thanks to the presence of different functional groups, further cyclizations were performed providing bicyclic polyoxygenated heterocycles