Metal-free synthesis of dihydrofuran derivatives as anti-vicinal amino alcohol isosteres.

Dihydrofuran cores are commonly incorporated into synthetically and pharmacologically significant scaffolds in natural product and drug discovery chemistry. Herein, we report a concise and practical strategy to construct spiro-dihydrofuran and amino dihydrofuran scaffolds as anti-vicinal amino alcohol isosteres. Hypervalent iodine (PhI(OAc)(NTs))-mediated C-H activation of alkynes resulted in two-bond formations with one pi bond cleavage: (i) C(sp)-N(sp) and O(sp)-C(sp); (ii) C(sp)-N(sp) and C(sp)-C(sp).

Positioning of an unprecedented 1,5-oxaza spiroquinone scaffold into SMYD2 inhibitors in epigenetic space.

Lysine methyltransferases are important regulators of epigenetic signaling and are emerging as a novel drug target for drug discovery. This work demonstrates the positioning of novel 1,5-oxaza spiroquinone scaffold into selective SET and MYND domain-containing proteins 2 methyltransferases inhibitors. Selectivity of the scaffold was identified by epigenetic target screening followed by SAR study for the scaffold.

Positioning of an unprecedented spiro[5.5]undeca ring system into kinase inhibitor space.

In-house 1,5-oxaza spiroquinone 1, with spiro[5.5]undeca ring system, was announced as an unprecedented anti-inflammatory scaffold through chemistry-oriented synthesis (ChOS), a chemocentric approach. Herein, we studied how to best position the spiro[5.