Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

Dušan Đ Škorić; Olivera R Klisurić; Dimitar S Jakimov; Marija N Sakač; János J Csanádi

doi:10.3762/bjoc.17.174

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

Beilstein J Org Chem. 2021 Oct 20:17:2611-2620. doi: 10.3762/bjoc.17.174. eCollection 2021.

Authors

Dušan Đ Škorić¹, Olivera R Klisurić², Dimitar S Jakimov³, Marija N Sakač¹, János J Csanádi¹

Affiliations

¹ Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
² Department of Physics, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 4, 21000 Novi Sad, Serbia.
³ Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Put Dr Goldmana 4, 21204 Sremska Kamenica, Serbia.

Abstract

A practical and high-yielding Schmidt reaction for the synthesis of fused tetrazoles from bile acid precursors was developed. Mild reaction conditions using TMSN₃ instead of hydrazoic acid as an azide source produced good yields of the desired tetrazoles. These conditions could be applied to other steroidal precursors. Additionally, an improved methodology for the synthesis of different ketone and enone precursors from cholic acid, deoxycholic acid, and chenodeoxycholic acid was established. Newly obtained tetrazole derivatives were characterized by NMR and X-ray diffraction spectroscopy. In a number of cases, preliminary antiproliferative tests of new compounds showed strong and selective activity towards certain tumor cell lines.

Keywords: Schmidt reaction; antiproliferative activity; steroids; tetrazoles; trimethylsilyl azide.

Grants and funding

The authors acknowledge the financial support of the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant No. 451-03-9/2021-14/200125).