posted on 2024-02-10, 14:30authored byMasahito Abe, Jeremy S. Coleman, Christopher C. Presley, Nathan D. Schley, Craig W. Lindsley
Sp3-enriched
small molecules play a critical role in
developing drug candidates. While designing analogues with greater
sp3 character, a methodology utilizing a less explored
cyclic-aziridine amide ring-opening reaction to generate sp3-enriched scaffolds has been developed and reported. This methodology
enables rapid access to substructures with higher fsp3 values,
attracting greater attention within the past few decades. The reaction
exhibits a wide reaction scope, featuring a highly sterically hindered
phenolic ether, thiophenolic ethers, protected aniline formations,
and aliphatic/heteroaromatic ring-containing aziridine amides as substrates.
Additionally, this reaction provides access to congested tertiary
ether formations through regioselective transformation, applicable
to an extensive range of drug discovery targets, construction of complex
small molecules, and natural product syntheses. The scaffolds developed
show improved physicochemical properties.