DEVELOPMENT OF PERORAL HYPOLIPIDEMIC FORMULATION BASED ON SULFATED ARABINOGALACTAN IN THE FORM OF POTASSIUM SALT

An original heparinoid, sulfated arabinogalactan in the form of potassium salt, possessing anticoagulant and hypolipidemic activities, has been developed at the A.E. Favorsky Irkutsk Institute of Chemistry Siberian Branch of the Russian Academy of Sciences.The aim was to develop solid peroral dose forms (capsules and film-coated tablets) for the prevention and treatment of atherosclerotic lesion of blood vessels on the basis of potassium salt of sulfated arabinogalactan which would be suitable for further clinical trials of these forms.Materials and methods. The following materials were used in the work: sulfated arabinogalactan in the form of potassium salt, obtained at the A.E. Favorsky Irkutsk Institute of Chemistry Siberian Branch of the Russian Academy of Sciences; Ludipress®; AEROSIL® 200 Pharma; calcium stearate; Aquacoat ECD. The powder mixtures were briquetted followed by tableting and application of the finished film coating Aquacoat ECD, and encapsulation in hard gelatin capsules.Results. Composition and technological characteristics of capsules and film-coated tablets were determined using physico-chemical and technological properties of sulfated arabinogalactan in the form of potassium salt. Technological parameters and quality indicators were determined for the solid pharmaceutical dose forms in accordance with the requirements of the State Pharmacopoeia of the Russian Federation of the XIVth edition. Conclusion. The optimum compositions and technology for the preparation of capsules and film-coated tablets based on potassium salt of sulfated arabinogalactan for the prevention and treatment of atherosclerotic lesion of blood vessels, were developed. The data obtained were used for the regulatory documentation design.

C–C Bond Construction: The Hou Synthesis of (−)-Brevipolide H

Yao Fu and Lei Liu of the University of Science and Technology of China devised (Chem. Eur. J. 2014, 20, 15334) conditions for the coupling of a halide 2 with a tosyl­ate 1 with inversion of absolute configuration, leading to 3. Hegui Gong of Shanghai University coupled (J. Am. Chem. Soc. 2014, 136, 17645) the glucosyl bromide 4 with an anhydride 5 to give the ketone 6. Luigi Vaccaro of the Università di Perugia showed (Org. Lett. 2014, 16, 5721) that TBAF promoted the opening of the epoxide 7 with the ketene silyl acetal 8, leading to the lactone 9. Valérie Desvergnes and Yannick Landais of the University of Bordeaux assembled (Chem. Eur. J. 2014, 20, 9336) the diketone 12 by using a Stetter catalyst to promote the conjugate addition of the acyl silane 11 to the enone 10. Thomas Werner of the Leibniz-Institute for Catalysis reported (Eur. J. Org. Chem. 2014, 6873) the enantioselective conversion of the prochiral triketone 13 to the bicyclic enone 15 by an intramolecular Wittig reaction, mediated by 14. Elizabeth H. Krenske of the University of Queensland and Christopher J. O’Brien also reported (Angew. Chem. Int. Ed. 2014, 53, 12907) progress (not illustrated) on catalytic Wittig reactions. Michael J. Krische of the University of Texas showed (J. Am. Chem. Soc. 2014, 136, 11902) that Ru-mediated addition of 17 to the aldehyde derived in situ from 16 gave 18 with high Z-selectivity. Vladimir Gevorgyan of the University of Illinois at Chicago constructed (J. Am. Chem. Soc. 2014, 136, 17926) the trisubstituted alkene 20 by the intramolecular Heck cyclization of 19. Kálmán J. Szabó of Stockholm University opti­mized (Chem. Commun. 2014, 50, 9207) the Pd-catalyzed borylation of the alkene 21 followed by in situ addition to the aldehyde 22 to give 23. Boris A. Trofimov of the Irkutsk Institute of Chemistry Siberian Branch devel­oped (Eur. J. Org. Chem. 2014, 4663) aqueous conditions for the preparation of a propargylic alcohol 26 by the addition of an alkyne 25 to the ketone 24. Huanfeng Jiang of the South China University of Technology prepared (Angew. Chem. Int. Ed. 2014, 53, 14485) the alkyne 28 by the oxidative elimination of the tosylhydrazone 27.

The development of original methodologies of directed synthesis of le-Carbs their analogs and precursors base donacetylene and its derivatives

New reactions, which have been discovered and continue to be developed in A.E. Favorsky Irkutsk institute of chemistry SB RAS on the basis of acetylene, a product of oil, gas and coal processing and multi-faceted building block for organic synthesis, have been considered. These reactions provide for the shortest routes to construction of fundamental heterocyclic scaffolds (pyrroles, imidazoles, pyrazoles, indoles, pyridines, dihydropyridines, etc.) with desirable and optimum combination of functional pharmacophoric groups and fragments, which are responsible for antiviral (HIV, flu), antitumor, tuberculostatic and hypotensive activities.