(6-Benzyloxy-2,5,7,8-tetramethylchroman-2-yl)acetaldehyde conjugates with 20-hydroxyecdysone, stachysterone B, and their 20,22-acetonides

Abstract

Conjugates consisting of ecdysteroid and α-tocopherol analog fragments were synthesized for the first time from 20-hydroxyecdysone and (6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl)acetaldehyde.Ecdysteroids (insect ecdysis, metamorphosis, and diapause hormones) are present not only in insect organisms, but also (in considerably higher concentrations) in plants from which these unique polyhydroxylated sterols were isolated. The properties and some chemical transformations of ecdysteroids were studied [1,2]. It was found that ecdysteroids are nontoxic for warm-blooded animals. Versatile physiological effect of ecdysteroids on humans and animals was revealed: they were found to control mineral, carbohydrate, lipid, and protein exchange, normalize sugar and cholesterol concentration in blood, stimulate hemopoietic activity, and exert immunomodulatory effect [3]. The diversity of physiological action of ecdysteroids is determined to some extent by their antioxidant properties, for many diseases are related to oxidative stress [4].We believed that a promising way of enhancing pharmacological effect of ecdysteroids may be conjugation with natural phenolic antioxidants such as α-tocopherol and its analogs. For this purpose, we examined reactions of 20-hydroxyecdysone (I) and its 2,3-and 20,22-acetonides II and III with (6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl)acetaldehyde (IV). The reaction of ecdysteroid I with 2 equiv of aldehyde IV, catalyzed by phosphomolybdic acid (PMA), gave 62% of the corresponding bis-adduct V (Scheme 1). This reaction occurred at a higher rate in the presence of p-toluenesulfonic acid as catalyst, but the yield of bis-acetal V did not change. Bis-adduct V was also formed in the reaction of 20-hydroxyecdysone 2,3-acetonide (II) with an equimolar amount of aldehyde IV in the presence of TsOH or PMA, but the yield was lower (35%). Under analogous conditions, from 20,22-acetonide III we obtained 60% of 2,3-adduct VI. Presumably, the formation of bis-adduct V from 2,3-acetonide II is favored due to known lability of compound II in acid medium [1].Apart from 20-hydroxyecdysone conjugates V and VI, from the reaction mixtures we isolated the corresponding 14,15-anhydro derivatives VII and VIII in 26 and 20% yield, respectively. Compounds VII and VIII can be regarded as analogous stachysterone B conjugates. 20-Hydroxyecdysone conjugates V and VI were subjected to debenzylation by hydrogenation over Pd/C in ethanol solution. As a result, the corresponding hydroxy derivatives IX and X were smoothly formed. The MALDI-TOF mass spectrum of bis-adduct IX contained [M + H] + ion peak. In the 1 H and 13 C NMR spectra of compounds V-X we observed signals from all protons iand carbon nuclei in the ecdysteroid and chroman fragments, in keeping with the assumed structure of their molecules.Monoadduct VI displayed in the 13 C NMR spectrum (in the region typical of acetal carbon atoms) signals from quaternary (δ C 106.97 ppm) and tertiary (δ C 101.97 ppm) carbon atoms in the 20,22-O-isopropylidene (cf. [5]) and eth...

Kinetics and mechanism of antioxidant action of polysubstituted tetrahydroquinolines in liquid‐phase oxidation reactions of organic compounds by oxygen

“…In the experiments, substances synthesized at the Institute of Petrochemistry and Catalysis of the Russian Academy of Sciences according to the procedure described in refs. [17][18][19] were used and were not subjected to additional purification.…”