UNUSUAL TRANSFORMATIONS OF THE MICHAEL ADDUCT OF LEVOGLUCOSENONE AND CYCLOHEXANONE

Abstract

Academician Genrikh Alexandrovich Tolstikov is a unique personality, a world-class scientist. During the years of his work as director of Institute of Organic Chemistry of the USC RAS (now the Ufa Institute of Chemistry of the Ufa Federal Research Center, Russian Academy of Sciences), new scientific directions were opened that are relevant and continue to this day. Research using sugars and anhydrous sugars, in particular, levoglucosane in the synthesis of prostaglandins and other bioactive structures, originates in the laboratory for the synthesis of low molecular weight bioregulators under the direction of prof. M.S. Miftakhov. After the creation of the laboratory for the synthesis of secondary metabolites (now the laboratory of pharmacophore cyclic systems) under the guidance of prof. Valeev F.A. Since the 90 s to the present, scientific research has been successfully conducted on the use of levoglucosenone and its derivatives in the synthesis of natural biologically active compounds and their analogues. Levoglucosenone attracted the attention of researches due to its availability and reactive, chiral structure. Its solubility in all organic solvents, and even in water, makes it a unique starting compound for organic synthesis. When describing the chemical behavior of levoglucosenone, it is important to note that many of its transformations proceed in a nontrivial manner and lead to unexpected products, which makes levoglucosenone an even more interesting object for study. Moreover, it turned out that the chemical transformations of its derivatives, in particular the Michael adducts of levoglucosenone and cycloalkanones, turned out to be even more unpredictable. This article is devoted to consideration of aspects of these transformations. Thus, it was found that two keto groups in the Michael adduct of levoglucosenone and cyclohexanone are not equivalent, the keto group of the carbohydrate fragment is more reactive. At the same time, when searching for the possibility of implementing intramolecular aldol condensation, it was unexpectedly found that the keto group of the carbohydrate fragment remains inert. Intramolecular carbocyclization could only be carried out in the Michael adduct of levoglucosenone and cyclododecanone. Based on the Michael adduct of levoglucosenone and cyclohexanone, a ten-membered lactone annelated with a carbohydrate fragment was synthesized. The problem of introducing substituents into the lactone cycle and modifying the carbohydrate part of the resulting lactone has been solved. On the basis of this adduct, an analog of the natural lactone, foracantholide, was synthesized. All results presented in the article include research conducted in our laboratory from 2014 to the present day.