Diastereoselective Synthesis of Triterpenoid 1,2,4-Trioxolanes by Griesbaum Co-ozonolysis

• Published in: Journal of natural products (Washington, D.C.) Vol. 82; no. 9; pp. 2550 - 2558
• Main Authors: Kazakova, Oxana B, Khusnutdinova, Elmira F, Petrova, Anastasiya V, Yamansarov, Emil Yu, Lobov, Alexander N, Fedorova, Alexandra A, Suponitsky, Kyrill Yu
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 27.09.2019; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Plant Sciences; Science & Technology; OXIDATION; ORGANIC PEROXIDES; ACID; KETOXIMES; CHEMISTRY; OZONE; DERIVATIVES
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.9b00393

Diastereoselective synthesis of triterpenoid 1,2,4-trioxolanes by Griesbaum co-ozonolysis was shown for the first time. Ozonolysis of 2-methoxyoximes (syn–anti-isomers mixture) of allobetulin or methyl oleanoate with CF3-ketones resulted in asymmetrical spiro-1,2,4-trioxolanes as mixtures of diastereomers in yields up to 80–85%. The configuration of the spiro-C-2 center of individual ozonides was determined by 2D NMR spectra and X-ray crystallographic analysis. The products of ozonolysis of triterpenoid 3-methoxyoximes were mixtures of regioisomeric N-methoxylactams. Thus, the fundamental differences in the oxidation of homologous triterpenoid 2- or 3-methoxyoximes with ozone have been established. These results may afford a new stage in the development of the Griesbaum method as applied to natural compounds and biologically active peroxides.