Synthesis and cytotoxic evaluation of beta-alkyl or beta-aryl-delta-methyl-alpha-methylene-delta-lactones. Comparison with the corresponding gamma-lactones.
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.
Albrecht
Lukasz
L
Institute of Organic Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924 Łódź, Poland.
Wojciechowski
Jakub
J
Albrecht
Anna
A
Wolf
Wojciech M
WM
Janecka
Anna
A
Studzian
Kazimierz
K
Krajewska
Urszula
U
Rózalski
Marek
M
Janecki
Tomasz
T
Krawczyk
Henryk
H
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation
D007783:Lactones