Synthesis of Abietane-derived Disulfides with Monosaccharide Fragments
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hesis of Abietane-derived Disulfides with Monosaccharide Fragments E. S. Izmest’eva,*, S. V. Pestovaa, S. A. Rubtsovaa, and A. V. Kuchina a
Institute of Chemistry, Komi Research Center, Ural Branch, Russian Academy of Sciences, Syktyvkar, 167000 Russia *e-mail: [email protected] Received March 19, 2020; revised March 29, 2020; accepted March 31, 2020
Abstract—A series of asymmetric disulfides was obtained in yields of 38–50% by the co-oxidation of a mixture of diterpene abietane-derived thiols and thiols synthesized from protected monosaccharides with galacto-, fructo-, and glucopyranose and ribofuranose fragments. After removal of the acetyl protection in the disulfide containing 1,2,3,4-tetra-O-acetyl-β-D-glucopyranose and dehydroabietane moieties, a disulfide with free glucose hydroxyl groups was obtained in a yield of 94%. Keywords: diterpenoids, monosaccharides, disulfides, thiols, oxidation
DOI: 10.1134/S1070428020080096
The disulfide bond S–S is quite a valuable functional group contained in various biologically active molecules with anticancer [1, 2], antifungal [3], and antioxidant activities [4]. The synthesis of asymmetric hydrolysisresistant disulfides, where one of the radicals serves as a target for binding to cellular protein receptors and the other acts as a biologically active fragment, is gaining special popularity in organic synthesis. For example, the galactose fragment is specific for the ASGT receptors of HepG2 liver cells, which activate endocytosis, thereby facilitating penetration of the lipophilic fragment of the molecule through the membrane into the cell [5]. The presence of a large amount of reduced glutathione (GSH) in the intracellular fluid results in inevitable rupture of the disulfide bond, while in the extracellular environment, where the GSH content is much lower, the disulfide bond can exist for a long time [6]. For this reason, disulfides are rarely found in the intracellular space and are not often used in pharmacology. At the same time, asymmetric disulfides with a monosaccharide as one of the fragments form, after the delivery and release of a biologically active molecule, free thiosaccharides which commonly do not show acute toxicity. In this connection the synthesis and study of novel disulfides containing two fragments with different is a relevant and perspective direction of research impor-
tant, in particular, for understanding the antimicrobial activity which can be associated with the interaction of the monosaccharide fragment with specific membrane surface receptors of pathogenic microorganisms. We earlier synthesized unsymmetrical disulfides containing, diisopropylidene-substituted galacto- and fructopyranose fragments, on the one hand, and a monoterpene fragment of the menthane, bornane, and pinane series on the other. It was shown that the synthesized disulfides do not exhibit hemolytic activity in a concentration of 10 μM and possess moderate antioxidant properties in relation to red blood cells of laboratory mice under conditions of H2O2-induced hemo
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