Next Article in Journal
Role of Stem Cells in Pathophysiology and Therapy of Spondyloarthropathies—New Therapeutic Possibilities?
Next Article in Special Issue
Expression and Interaction Analysis among Saffron ALDHs and Crocetin Dialdehyde
Previous Article in Journal
Anti-Inflammatory and Skin Barrier Repair Effects of Topical Application of Some Plant Oils
Previous Article in Special Issue
Evaluation of Biosynthesis, Accumulation and Antioxidant Activityof Vitamin E in Sweet Corn (Zea mays L.) during Kernel Development
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(1), 81; https://doi.org/10.3390/ijms19010081

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

1
Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös utca 6, Hungary
2
Department of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, Eötvös utca 6, Hungary
3
Interdisciplinary Centre of Natural Products, University of Szeged, H-6720 Szeged, Eötvös utca 6, Hungary
4
Stereochemistry Research Group of the Hungarian Academy of Sciences, H-6720 Szeged, Eötvös utca 6, Hungary
*
Author to whom correspondence should be addressed.
Received: 12 December 2017 / Revised: 21 December 2017 / Accepted: 22 December 2017 / Published: 28 December 2017
(This article belongs to the Special Issue Molecular Transformations of Natural Products)
View Full-Text   |   Download PDF [1028 KB, uploaded 28 December 2017]   |  

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. View Full-Text
Keywords: terpenoid; stereoselective; 1,2,4-oxadiazole; 1,3,4-oxadiazole; chiral catalyst; diethyl zinc; antiproliferative activity terpenoid; stereoselective; 1,2,4-oxadiazole; 1,3,4-oxadiazole; chiral catalyst; diethyl zinc; antiproliferative activity
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Share & Cite This Article

MDPI and ACS Style

Gonda, T.; Bérdi, P.; Zupkó, I.; Fülöp, F.; Szakonyi, Z. Stereoselective Synthesis, Synthetic and Pharmacological Application of Monoterpene-Based 1,2,4- and 1,3,4-Oxadiazoles. Int. J. Mol. Sci. 2018, 19, 81.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top