Abstract
The present study describes an AuPPh3Cl/AgSbF6-catalyzed cascade reaction between amine nucleophiles and alkynoic acids in water. This process proceeds in high step economy with water as the sole coproduct, and leads to the generation of two rings, together with the formation of three new bonds in a single operation. This green cascade process exhibits valuable features such as low catalyst loading, good to excellent yields, high efficiency in bond formation, excellent selectivity, great tolerance of functional groups, and extraordinarily broad substrate scope. In addition, this is the first example of the generation of an indole/thiophene/pyrrole/pyridine/naphthalene/benzene-fused N-heterocycle library through gold catalysis in water from readily available materials. Notably, the discovery of antibacterial molecules from this library demonstrates its high quality and potential for the identification of active pharmaceutical ingredients.
Highlights
Rapid advances in genomics and proteomics have resulted in the identification of an increasing number of novel therapeutic targets [1,2,3,4,5], and the existing compound libraries can no longer well meet the needs of drug screening
To the best of our knowledge, this is the first example of the generation of privileged substructure-based diversity-oriented synthesis (pDOS) compound library encompassing skeletal diversity, molecular complexity, and drug-like properties through gold catalysis in water
A green and general tandem reaction between alkynoic acids and amine nucleophiles through gold catalysis in water has been developed. This process proceeds with high efficiency leading to the formation of two rings and three new bonds in a single operation
Summary
Rapid advances in genomics and proteomics have resulted in the identification of an increasing number of novel therapeutic targets [1,2,3,4,5], and the existing compound libraries can no longer well meet the needs of drug screening. Considering the structurally diverse targets in a wide “biological space”, high-throughput screening (HTS) of skeletally diverse compounds, which occupy a broader “chemical space”, can apparently enhance the hit rates [9,10]. In addition to skeletal diversity, drug-like properties of the compounds are important for the generation of high-quality compound libraries [11,12,13,14], which can increase the possibility of identifying drug-like hit compounds. As a result, privileged structures have received wide attention in drug discovery because they are widely found in natural and pharmaceutical products [15,16,17,18,19].
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