Stereocontrolled intramolecular transformations of (-)-α santonin

Keywords: sesquiterpene γ-lactone, eudesmanolide, α-santonin, base, keto-eudesmane ether, stereoselectivity, electrophilic rearrangements, intramolecular transformations


Chemical transformations of eudesmane sesquiterpene γ-lactones, leading to new biologically active compounds, have become an important direction in medicinal chemistry. This article discusses the stereoscopic intramolecular transformations of the sesquiterpene γ-lactone of the eudesmanic structure (-)-α santonin, a perspective natural compound characterized by a wide spectrum of biological activity.Stereoselective synthesis of new practically significant cis-condensed keto-eudesmane esters and ethylated santonin derivatives was carried out at room temperature in an argon atmosphere by the reaction of α-santonin with methyl and ethyl alcohols and alkyl halides in the presence of the Me3CONa-DMF base. It was revealed that, under the reaction conditions, the initial stage of santonin carbanion formation initiates subsequent stages of intramolecular electrophilic rearrangements with the formation of anenolate ion, which futhur interacts stereoselectively with nucleophilic and electrophilic reagents.It was shown that the synthesis of C4-α-ethyl-santonin with a six-membered ring configuration in the form of a distorted chair-chair can serve as a confirmation of the proposed mechanism of formation of practically valuable 6-keto-eudesmane ethers. In this article, the structure and spatial structure of the synthesized compounds is established using modern physicochemical and spectroscopic (1H NMR, 2D COZY NMR, NOESY, mass-spectrometry and X-ray structural analysis) research methods.


1 Merkhatuly N, Zhokizhanova SK, Balmagambetova LT, Adekenov SM (2007) Russ J Org Chem 43(1):150-151. Crossref

2 Merkhatuly N, Abeuova SB, Iskanderov AN, Omarova AT, Toktarova LN (2015) Rus J Org Chem 51(1):1664-1665. Crossref

3 Barrero AF, Rosales A, Cuerva JM, Oltra JE (2003) Org Lett 5(11):1935-1938. Crossref

4 Seaman FC (1982) Botanical Rev 48(2):121-595. Crossref

5 Wang J, Su S, Zhang S, Zhai S, Sheng R, Wu W, Guo R (2019) Eur J Med Chem 175:215-233. Crossref

6 Li Sh, Ding J, Li Sh (2018) Phytochem Lett 24:102-104. Crossref

7 Romanucci V, Fabio G, Marino C, Davinelli S, Scapagnini G, Zarrelli A. (2018) Phytochem Lett 23:116-119. Crossref

8 Sun L, Wang Zh, Wang Y, Xu J, He X (2020) Fitoterapia 142:104-452. Crossref

9 Sakipova Z, Giorno Т, Bekezhanova T, Wong N, Shukirbekova A, Fernandes P, Boylan F (2020) Molecules 25:2728-2733. Crossref

10 Liu X, Li H, Wang Sh, Zhang J, Liu D (2021) Chinese Herb Medicines 13:167-176. Crossref
How to Cite
Iskanderov, A., Vojtisek, P., Zhokizhanova, S., Jadenova, A., & Merkhatuly, N. (2022). Stereocontrolled intramolecular transformations of (-)-α santonin. Chemical Bulletin of Kazakh National University, 104(1), 44-49.