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PC-11

Divergent synthesis of natural heterotricyclic frameworks from gamma-

alkynyl-1,3-diketones via base-mediated tandem

2
,2
2
2
Y u -Qi Wang, Ming-Yang Chang, Fang-Yi Jen, Yi-En Liang, Hsi Ho, Wen-Tai Li*
2
1

1 College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University
2 National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei
112304, Taiwan
* E-mail: wtli@nricm.edu.tw

Abstract
A novel base-mediated strategy for the divergent synthesis of oxygen- and nitrogen-
containing heterotricyclic frameworks, furo[3,2-c]chromenes, xanthones, and furo[3,2-
c]quinolones, from γ-alkynyl 1,3-diketones was presented. These one-pot tandem reactions
exhibit high versatility, proceeding via base-mediated O-attack through 5-exo-dig or C-attack
intramolecular cyclization onto the alkyne, or through sequential regioselective condensation
followed by tandem annulation. Precise control of reaction conditions enables selective
annulation pathways, providing efficient access to diverse heterocyclic scaffolds with
pharmaceutical potential. Inspired by isodictamnine, a natural [6,6,5]-fused furoquinolinone
from Dictamnus angustifolius with reported anti-inflammatory and anti-cancer activities, we
developed a synthetic route to prepare related novel derivatives. Palladium-catalyzed
intramolecular cyclization formed the furan ring, followed by base-mediated quinolinone ring
construction in one pot. Thiophene analogues were obtained via Lawesson’s reagent-mediated
thionation and cyclization. Biological evaluation showed that furan-containing derivatives
significantly reduced LPS-induced inflammation in BV-2 microglial cells, while thiophene
analogues exhibited potent cytotoxicity against A549 lung cancer cells, underscoring their
potential as anti-inflammatory and anti-cancer agents.

Keywords: Anti-cancer activity; Furo[3,2-c]chromene; Xanthone; Isodictamnine