Glycoconjugates via Phosphorus Ylides

A facile, high yielding access to rare chimeric compounds combining phosphorus ylides with complex glycosyl formamides is described. We determined X-ray structures gaining structural insight into this compounds class. In addition, data mining of similar compounds deposited within the Cambridge Structural Database was performed. These derivatives could be used either as synthetic intermediates via the ylide functionalization and glyco chemical biology synthons or improving the pharmacokinetic properties of a potential bioactive molecule, exploiting the glycosyl moiety

Multicomponent Reactions:"Kinderleicht"

A demonstration experiment of the synthesis of a novel tetrazole derivative via a multicomponent reaction (Ugi tetrazole four component reaction, UT-4CR) bearing a luminol moiety and a subsequent exploitation of its chemiluminescent properties is described. A complex product is generated in just one simple step, so simple that children can do it: "kinderleicht", German for dead easy. Students are stimulated, inspired, and involved in a multilevel active learning process using the Steps to Inquiry framework as a metacognitive tool that raises student awareness regarding scientific process and prompts them to ask their own questions discussing the merits of a mechanism and evaluating its effectiveness before they start their own cycles of inquiry

Sustainable multicomponent indole synthesis with broad scope

The most preferred heterocyclic indole core was de novo assembled by an innovative 2-step reaction from inexpensive and broadly available anilines, glyoxal dimethyl acetal, formic acid and isocyanides involving an Ugi multicomponent reaction followed by an acid induced cyclization. As opposed to many other indoles syntheses, our method delivers under mild and benign conditions using ethanol as solvent and no metal catalyst. The scope of the reactions was scouted and 20 derivatives are described

Fluorene-Based Multicomponent Reactions

Fluorene and fluorenone are privileged structures with extensive utility in both materials science and drug discovery. Here, we describe syntheses of those moieties through isocyanide-based multicomponent reactions (IMCRs) and the incorporation of the products in diverse and complex derivatives that can be further utilized. We performed six different IMCRs, based on the dual functionality of 9-isocyano-9H-fluorene, and we describe 23 unprecedented adducts

A multicomponent tetrazolo indole synthesis

The ubiquitous presence of the indole fragment in natural products and drugs asks for ever novel syntheses. We report an unprecedented mild, two-step synthesis of 2-tetrazolo substituted indoles based on the Ugi-tetrazole reaction combined with an acidic ring closure. A gram-scale synthesis, a bioactive compound and further transformations were performed

Tetrazoles via Multicomponent Reactions

Tetrazole derivatives are a prime class of heterocycles, very important to medicinal chemistry and drug design due to not only their bioisosterism to carboxylic acid and amide moieties but also to their metabolic stability and other beneficial physicochemical properties. Although more than 20 FDA-approved drugs contain 1 H- or 2 H-tetrazole substituents, their exact binding mode, structural biology, 3D conformations, and in general their chemical behavior is not fully understood. Importantly, multicomponent reaction (MCR) chemistry offers convergent access to multiple tetrazole scaffolds providing the three important elements of novelty, diversity, and complexity, yet MCR pathways to tetrazoles are far from completely explored. Here, we review the use of multicomponent reactions for the preparation of substituted tetrazole derivatives. We highlight specific applications and general trends holding therein and discuss synthetic approaches and their value by analyzing scope and limitations, and also enlighten their receptor binding mode. Finally, we estimated the prospects of further research in this field

Multicomponent reaction-derived covalent inhibitor space

The area of covalent inhibitors is gaining momentum due to recently introduced clinical drugs, but libraries of these compounds are scarce. Multicomponent reaction (MCR) chemistry is well known for its easy access to a very large and diverse chemical space. Here, we show that MCRs are highly suitable to generate libraries of electrophiles based on different scaffolds and three-dimensional shapes and highly compatible with multiple functional groups. According to the building block principle of MCR, acrylamide, acrylic acid ester, sulfurylfluoride, chloroacetic acid amide, nitrile, and alpha,beta-unsaturated sulfonamide warheads can be easily incorporated into many different scaffolds. We show examples of each electrophile on 10 different scaffolds on a preparative scale as well as in a high-throughput synthesis mode on a nanoscale to produce libraries of potential covalent binders in a resource-and time-saving manner. Our operational procedure is simple, mild, and step economical to facilitate future covalent library synthesis