Conformationally restricted goniofufurone mimics with halogen, azido or benzoyloxy groups at the C-7 position: Design, synthesis and antiproliferative activity

Abstract

© 2018 Elsevier Ltd A series of new conformationally restricted goniofufurone mimics, bearing an additional 1,3-dioxan ring and a halogen, azido or benzoyloxy functionality at the C-7 position has been designed and synthesized. The Appel reaction was used for replacement of 7-OH group with Cl or Br functions in tricyclic lactone (3). 7-Iodo derivative (3d) was prepared by using the Ph3P/I2/2,6-lutidine reagent system. 7-Fluoro group was introduced by treatment of 3 with DAST, while the corresponding 7-azido and 7-benzoyloxy derivatives have been prepared by multistep sequences. Synthesized products were evaluated for their ability to inhibit growth of selected human malignant cell lines. Structure-activity relationships demonstrated that the nature of a substituent at the C-7 position could enhance the antiproliferative activity of the analogues. The preliminary study on the mechanisms indicated that all synthesized compounds induced apoptosis in 61–77% of K562 cells.