Sulfur/selenium-containing electron-rich arenes (ERAs) exist in a wide range of both approved and investigational drugs with diverse pharmacological activities. These unique chemical structures and bioactive properties, if combined with the...
The functionalized 4H-pyran scaffold has aroused synthetic attention because it is widely found in many interesting pharmacologically relevant compounds. We here disclose its incorporation into DNA-encoded chemical libraries, combining this scaffold with the merits of scaffold architecture in drug design. Under the optimized DNA-compatible conditions, functionalized 4H-pyrans were efficiently formed with a broad substrate scope. Among the 4Hpyrans formed, the axial structure features rotational restriction, and the spirocyclic structure provides rigidity and three-dimensionality. These efforts open the door for the construction of DNA-encoded chemical libraries with more consideration for this structural architecture.
As
a powerful platform in drug discovery, the DNA-encoded chemical
library technique enables the generation of numerous chemical members
with high structural diversity. Epoxides widely exist in a variety
of approved drugs and clinical candidates, eliciting multiple pharmaceutical
activities. Herein, we report a non-oxidative DNA-compatible synthesis
of di-/trisubstituted α,β-epoxyketones by implementing
aldehydes and α-chlorinated ketones as abundant building blocks.
This methodology was demonstrated to cover a broad substrate scope
with medium-to-excellent conversions. Further structural diversification
and transformation were also successfully explored to fully leverage
α,β-epoxyketone moiety.
We present the development of an efficient synthetic route to generate a DNA-compatible vinyl sulfone functional group, and the subsequent chemical transformations demonstrated the feasibility of our method in DEL construction.
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