Chemo- and Diastereoselective Cycloisomerization/[2 + 3] Cycloaddition of Enynamides: Synthesis of Spiropyrazolines as Potential Anticancer Reagents

Abstract

A silver-catalyzed one-pot cycloisomerization/[2 + 3] cycloaddition of enynamides with in situ generated nitrile imines has been developed. Unlike the well-established cycloisomerization/[4 + n] cycloadditions of enynamides, this strategy provides efficient access to a new type of spiropyrazolines, which exhibit an anti-proliferation effect on multiple tumor cell lines. The compound 3u exhibits obvious anticancer activity by inducing apoptosis in RKO cells. The combination of compound 3u and an autophagy inhibitor could improve its anti-proliferation capacities.

Asymmetric construction of enantioenriched furo[2,3-b]pyridines through sequential gold, palladium/phosphoric acid catalysis

“…Enynamides 1 , a class of readily accessible substrates, are liable to undergo 5- endo-dig cyclization in the presence of a π-Lewis acid catalyst, such as Au( i ) 5 and Ag( i ). 6 The resultant dihydrofuran-derived azadiene species I could serve as highly reactive 4π-components to assemble with various catalytically generated dipole-type intermediates, including N-heterocyclic carbene (NHC)-tethered enolates and homo-enolates, 7 enamines derived from aldehydes, 8 and π-allylpalladium-containing dipolar species, 9 furnishing various fused heterocycles enantioselectively (Scheme 1a). Recently, our group discovered that Pd 0 could function as an efficient π-Lewis base catalyst to increase the HOMO energy of various conjugated diene systems upon forming η 2 -complexes with them.…”