Stereoselective Synthesis, Synthetic and Pharmacological Application of Monoterpene-Based 1,2,4- and 1,3,4-Oxadiazoles

Abstract

Stereoselective synthesis of monoterpene-based 1,2,4- and 1,3,4-oxadiazole derivatives was accomplished starting from α,β-unsaturated carboxylic acids, obtained by the oxidation of (−)-2-carene-3-aldehyde and commercially available (−)-myrtenal. 1,2,4-Oxadiazoles were prepared in two steps via the corresponding O-acylamidoxime intermediates, which then underwent cyclisation induced by tetrabutylammonium fluoride (TBAF) under mild reaction conditions. Stereoselective dihydroxylation in highly stereospecific reactions with the OsO4/NMO (N-methylmorpholine N-oxide) system produced α,β-dihydroxy 1,2,4-oxadiazoles. Pinane-based 1,3,4-oxadiazoles were obtained similarly from acids by coupling with acyl hydrazines followed by POCl3-mediated dehydrative ring closure. In the case of the arane counterpart, the rearrangement of the constrained carane system occurred with the loss of chirality under the same conditions. Stereoselective dihydroxylation with OsO4/NMO produced α,β-dihydroxy 1,3,4-oxadiazoles. The prepared diols were applied as chiral catalysts in the enantioselective addition of diethylzinc to aldehydes. All compounds were screened in vitro for their antiproliferative effects against four malignant human adherent cell lines by means of the MTT assay with the O-acylated amidoxime intermediates exerting remarkable antiproliferative action.

New Deoxycholic Acid Derived Tyrosyl-DNA Phosphodiesterase 1 Inhibitors Also Inhibit Tyrosyl-DNA Phosphodiesterase 2

“…Activation of the carboxyl group in compound 1 with CDI and subsequent reaction with amidoximes containing the para -bromophenyl moiety led to the formation of intermediates 12 and 14 with 77% and 80% yields, respectively. 1,2,4-Oxadiazole derivatives 13 and 15 were formed by intermediates 12 and 14 cyclization in the presence of TBAF, an effective catalyst for the preparation of 1,2,4-oxadiazoles [ 28 ], under reflux in THF with 58% and 89% yields after purification by column chromatography.…”

5-[5-(4-Chlorophenyl)isoxazol-3-yl]-N-phenyl-1,3,4-oxadiazol-2-amine

“…Substituted 1,3,4-oxadiazol-2-amines can act as anticancer and antiproliferative agents (Ahsan et al, 2014;Gonda et al, 2017;Kumar et al, 2009Kumar et al, , 2011. As part of our studies in this area, we now describe the synthesis and structure of the title compound.…”

Monoterpenes and Their Derivatives—Recent Development in Biological and Medical Applications

“…However, this molecule exhibited lower antiproliferative activities against the triple-negative breast cancer cell line (MDA-MB-231) than other cell lines used in gynecology. Unfortunately, the other compounds 78 – 82 exhibited a visibly weaker action against the ovarian cancer cell line (A2780) ( Figure 17 ) [ 72 ].…”