No abstract

SummaryTaking into consideration the biological activity of the only natural products containing a 1,2,4-oxadiazole ring in their structure (quisqualic acid and phidianidines A and B), the natural product analogs 1-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenyl)pyrrolidine-2,5-dione (4) and 1-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenyl)-1H-pyrrole-2,5-dione (7) were synthesized starting from 4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)aniline (1) in two steps by isolating the intermediates 4-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenylamino)-4-oxobutanoic acid (3) and (Z)-4-(4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)phenylamino)-4-oxobut-2-enoic acid (6). The two natural product analogs 4 and 7 were then tested for antitumor activity toward a panel of 11 cell lines in vitro by using a monolayer cell-survival and proliferation assay. Compound 7 was the most potent and exhibited a mean IC50 value of approximately 9.4 µM. Aniline 1 was synthesized by two routes in one-pot reactions starting from tert-butylamidoxime and 4-aminobenzoic acid or 4-nitrobenzonitrile. The structures of compounds 1, 2, 4, 5 and 6 were confirmed by X-ray crystallography.

This work presents the synthesis, characterization, and application of several new metal(I) complexes with trifluoromethylpyridine-containing N-heterocyclic carbene (NHC) ligands. The metal of choice was gold(I) for compounds 7 -10, rhodium(I) for 11 -12, and iridium(I) for 13 -14, respectively. The trifluoromethylpyridine moiety was incorporated, along with other biologically active moieties, with the intention of modifying the lipophilicity of the complexes, so that the transport of the active units (M-NHC) through the cell wall barrier is facilitated. The biological activity of the complexes was investigated. In vitro assessment of antitumor activity in a panel of 12 human tumor cell lines by a monolayer assay revealed good potency (mean IC 50 12.6 lM) and tumor selectivity for one compound. The solid-state structures of two solvates of compound 7, one with MeOH and one with THF, were determined by X-ray diffraction analysis.

New chiral derivatives of 1 5 ,3 5 ,5 5 ,7 5 -tetra-tert-butyl-1,3,5,7(1,3)-tetrabenzenacyclooctaphane-1 2 ,3 2 ,5 2 ,7 2 -tetraol [(1); tert-butyl-calix[4]-arene] were synthesized by coupling modified chiral quinuclidines derived from the natural-product-based alkaloids quincorine and quincoridine with the calix[4]arene 1 via either an ester bond or an amide bond. X-ray analyses of two products were performed. Applications of the products in asymmetric catalytic hydrogen transfer reactions are described. A protocol is presented to multi-substitute calix [4] arene at the methylene bridges, resulting in, e.g., 2,6-carboxyl-all-tert-butyl all-methoxy-calix[4]arene.