Branching cascades provide access to two amino-oxazoline compound libraries

Abstract

An efficient synthetic access to two amino-oxazoline compound libraries was developed employing the branching cascades approach. A common precursor, that is, chromonylidene β-ketoester was transformed into two different ring-systems, that is, the pyridine and the benzopyrane substituted hydroxyphenones. In further two steps, the ketone moiety in two ring-systems was transformed into an amino-oxazoline ring. The functional groups on the two amino-oxazoline scaffolds were exploited further to generate, a compound collection of ca. 600 amino-oxazolines which are being exposed to various biological screenings within the European Lead Factory consortium.

Expansion of chemical space for collaborative lead generation and drug discovery: the European Lead Factory Perspective

“…Indeed, a significant number of unprecedented spiro, bridged, and fused polycycles with different degrees of saturation, conjugation, and substitution have been synthesized and expanded to a library format. This has been recently exemplified by several publications from the ELF chemistry groups detailing the associated design and validation aspects [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Given that most theoretical ring systems remains unexplored [39], the synthesis of novel rings represents one of the strategies embraced by the ELF chemistry consortium to expand the available chemical space.…”

The European lead factory—an experiment in collaborative drug discovery

“…These challenges notwithstanding, the scientists of ELF Chemistry Consortium have developed key approaches that can facilitate novel bioactive molecule discovery, including diversity-oriented synthesis, biology-oriented synthesis, multicomponent chemistry and activity-directed synthesis, as recently described for selected examples [23][24][25][26][27][28][29][30][31][32][33][34] . The innovative chemical approaches taken by the ELF Chemistry Consortium are yielding novel, diverse and distinctive compounds that will complement existing large compound collections used for high throughput screening drug discovery applications, thus serving as a blueprint for future compound collection enhancement campaigns.…”

Microwave-Assisted Branching Cascades: A Route to Diverse 3,4-Dihydroquinazolinone-Embedded Polyheterocyclic Scaffolds

“…The major advantage of this approach is that diversity is generated in a one-step/pot process by treating one or more polyfunctionalized precursors with different reagents/reactants or under various reaction conditions. Kumar and co-workers used chromone-based precursors and more recently a de novo branching cascades approach to access complex molecular frameworks . The O’Connell and Stockman groups reported a 12-fold branching pathway to access diverse natural product-like polycyclic scaffolds from a single keto-diester intermediate .…”