Synthesis and biological activity of new thiazole isosteres of goniofufurone and 7-epi-goniofufurone

Abstract

(+)-Goniofufurone is the naturally occurring cytotoxic styryl lactone isolated from the stem bark of Goniothalamus giganteus (Annonaceae) that possesses structure marked by furano-furone bicyclic core. Herein we report a total synthesis of two novel (7-epi-)goniofufurone isosteres bearing a 2-thiazolyl-4-carboxylic acid ethyl ester moiety instead of the aromatic ring at C-7. The key intermediate (4) was obtained by addition of trimethylsilyl cyanide to known aldehyde 3, which was readily available from D-glucose through a modified literature procedure. Thiazole ring was introduced in two consecutive steps (e, f), which included cyclization and oxidation, respectively, while the γ-lactone function was built in the penultimate step (h), after the deprotection of hydroxyl groups at positions C-1 and C-2 (g). After removal of benzyl protection (i), final products 1 and 2 were obtained. Antiproliferative activity of both analogues against a number of tumor cell lines will be presented.