Synthesis and cytotoxic evaluation of beta-alkyl or beta-aryl-delta-methyl-alpha-methylene-delta-lactones. Comparison with the corresponding gamma-lactones

Lukasz Albrecht; Jakub Wojciechowski; Anna Albrecht; Wojciech M Wolf; Anna Janecka; Kazimierz Studzian; Urszula Krajewska; Marek Rózalski; Tomasz Janecki; Henryk Krawczyk

doi:10.1016/j.ejmech.2009.11.018

Synthesis and cytotoxic evaluation of beta-alkyl or beta-aryl-delta-methyl-alpha-methylene-delta-lactones. Comparison with the corresponding gamma-lactones

Eur J Med Chem. 2010 Feb;45(2):710-8. doi: 10.1016/j.ejmech.2009.11.018. Epub 2009 Nov 14.

Authors

Lukasz Albrecht¹, Jakub Wojciechowski, Anna Albrecht, Wojciech M Wolf, Anna Janecka, Kazimierz Studzian, Urszula Krajewska, Marek Rózalski, Tomasz Janecki, Henryk Krawczyk

Affiliation

¹ Institute of Organic Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924 Łódź, Poland.

PMID: 19962797
DOI: 10.1016/j.ejmech.2009.11.018

Abstract

We present a simple and general strategy for the synthesis of beta,delta-disubstituted-alpha-methylene-delta-lactones starting from easily available tert-butyl 2-(diethoxyphosphoryl)alk-2-enoates. The elaborated synthetic protocol includes pyrrolidine-catalyzed Michael addition of acetone, diastereoselective reduction of the carbonyl group, lactonization and finally the Horner-Wadsworth-Emmons reaction with formaldehyde. All alpha-methylene-delta-lactones were evaluated in vitro against mouse leukemia cell line L-1210 and two human leukemia cell lines HL-60 and NALM-6. Comparison of cytotoxic activity with corresponding alpha-methylene-gamma-lactones is also discussed.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Cell Proliferation / drug effects
Humans
Lactones / chemical synthesis*
Lactones / chemistry
Lactones / pharmacology*
Mice
Models, Molecular
Molecular Conformation

Substances

Lactones