Enantioselective synthesis and cytotoxic evaluation of 4,5-dihydro-5-[aryl(hydroxy)methyl]-3-methylidenefuran-2(3H)-ones.
A series of enantiomerically enriched 4,5-dihydro-5-[aryl(hydroxy)methyl]-3-methylidenefuran-2(3H)-ones (8) were synthesized by means of asymmetric Sharpless dihydroxylation of the 2-phosphorylated 5-aryl-pent-4-enoic acids 13, followed by Horner-Wadsworth-Emmons reaction of the resulting furanones 15 (Scheme 2). An enantiomeric excess (ee) of 20-95% was achieved for compounds 8, and their absolute configurations were determined by the Mosher ester method. Cytotoxic evaluation against L-1210 and HL-60 leukemia cell lines revealed that the target compounds 8 are active in the micromolar concentration range (Table 2). Thereby, significant differences in activity between the corresponding enantiomers were observed for the HL-60 cell line.
Janecki
Tomasz
T
Institute of Organic Chemistry, Technical University of Łódź, Zeromskiego 116, PL-90-924 Łódź. tjanecki@p.lodz.pl
Albrecht
Anna
A
Warzycha
Edyta
E
Studzian
Kazimierz
K
Janecka
Anna
A
Krajewska
Urszula
U
Rózalski
Marek
M
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007783:Lactones; D012717:Sesquiterpenes