Synthesis and Biological Activity of Alkane-1,1-diylbis(phosphonates) of Diterpenoid Isosteviol

Abstract

Isosteviol reacted with α,ω-dibromoalkanes to give 19-(ω-bromoahkyl) esters which were treated with tetraethyl methylenebis(phosphonate) to obtain bis(phosphonates) conjugated to the deterpenoid skeleton through a polymethylene spacer. The bis(phosphonates) were converted to the corresponding bis(phosphonic acids) by transformation to trimethylsilyl esters and subsequent methanolysis. One of the synthesized compounds showed a high antimicrobial activity (MIC 3.9 µg/mL) against S. aureus and a high cytotoxicity (IC₅₀ 15–18 µM) toward M-HeLa and MCF-7 human cancer cell lines.