Silver‐Catalyzed Tandem Reaction of β‐Alkynyl Ketones toward Spiro[isochromene‐1,4′‐quinoline] with Anticancer Activities

Abstract

Spirocyclic frameworks could enhance the drug-like properties of planar bioactive molecules by increasing their three-dimensionality, making the development of synthetic methodology and bioactivity assays for spiro compounds highly attractive. This work reported the silver-catalyzed tandem cycloisomerization/Povarov reaction between β-alkynyl ketones and hexahydro-1,3,5-triazines, access to spiro[isochromene-1,4'-quinoline]. This synthetic protocol was characterized by remarkable efficiency, low catalyst-loading and high diastereoselectivity. Moreover, the spirocyclic quinolines exhibited good cytotoxicity in U937 cells by activating the Notch-signaling pathway exclusively.

Substituent-controlled divergent cyclization reactions of benzo[c][1,2]dithiol-3-ones and hexahydro-1,3,5-triazines

“…3 As documented in the literature, hexahydro-1,3,5-triazines could act as bench-stable surrogates of formaldimines to access secondary amines via aminomethylations or Mannich-type reactions. 4 Apart from the assembly of amines, hexahydro-1,3,5-triazines are frequently harnessed as prominent two-, 5 three-, 6 and four-atom 7 building blocks in cycloaddition reactions to forge a vast array of N-heterocycles in a single-vessel reaction. Moreover, hexahydro-1,3,5-triazines were also sporadically utilized as five- 8 and six-atom 9 synthons to produce hexahydropyrimidines under mild conditions.…”