One-Pot Multi-Reaction Processes: Synthesis of Natural Products and Drug-Like Scaffolds

Abstract

Abstract:One-pot multi-reaction processes involving Overman rearrangements, metathesis cyclizations, and Diels-Alder reactions have been developed for the rapid and efficient synthesis of aminosubstituted carbocyclic and heterocyclic compounds. This account describes the development and optimization of these processes, as well as their applications in the synthesis of natural products and drug-like scaffolds.

Synthesis and pharmacological characterization of UVI3502, a novel cannabinoid receptor 1 (CB1) antagonist/inverse agonist

“…For the synthesis of the compounds, we have increased further the efficiency of the intramolecular oxidative Heck cascade reaction (Denis et al, 2015), by incorporating a Sonogashira cross-coupling prior to the heterocyclization–Heck, as described for other heterocycles, which led to the formation and N -cyclization of o -alkynylaniline intermediates starting from appropriately protected ortho -iodoanilines and terminal alkynylanilines. The sequence of chemical transformations took place in the same reaction flask while additional reagents and catalysts were added at different time intervals (Calder et al, 2014), another example of the ‘one-pot’ multi-component reaction (MCR) (Weber, 2002). This combination of consecutive Sonogashira, nucleopalladation and oxidative Heck couplings conveniently allowed the preparation of a new series of 7,12-dihydroindolo[3,2-d]benzazepine-6(5 H )-ones.…”

A one-pot telescopic synthesis of benzo[b]carbazoles and exploration of their liquid crystalline properties

“…One-pot multistep synthesis is a powerful synthetic tool to assemble complex molecules in a short and efficient manner. 6 Although the one-pot transformations can be atom-economical and can minimize the difficulties involved in the purification and isolation of the intermediates, the development of such processes is more complex than originally perceived. The compatibility of the substrates and the intermediates with different reagents and reaction conditions often dictates the selectivity and efficiency of the overall transformation.…”