No abstract

Levoglucosenone has established itself as a good Michael acceptor and a powerful dienophile in Diels-Alder reactions, dipolar cycloaddition and in a number of other transformations. In the Diels-Alder reactions of levoglucosenone with 1,3-dienes, chiral derivatives of cyclohexene are obtained, which are valuable products for the synthesis of natural compounds. We previously studied the reaction of the interaction of levoglucosenone with Dane diene under catalytic, thermal conditions, at ultrahigh pressures and microwave irradiation. It was found that as a result of the reaction, 2 adducts are formed – (1S,2S,15S,17R)-9-methoxy-18,20-dioxapentacyclo[15.2.1.02,15.0.5,14.06,11]icosa-4,6,8, 10-tetraen-16-one and its isomer, the product of the double bond migration is (1S,2S,14S,15S,17R)-9-methoxy-18,20-dioxapentacyclo[15.2.1.02,15.0.5, 14.06,11]icosa-5(14), 6,8,10-tetraen-16-one. In this work, we have developed methods for the transformation of these Diels-Alder adducts in approaches to compounds with a steroid skeleton. Thus, based on the obtained Diels-Alder adducts, optically active hydrazone was synthesized. An optimal method for deoxygenation of a keto group proceeding by aromatization of cycle B in (1S,2S,14S,15S,17R)-9-methoxy-18,20-dioxapenta-cyclo[15.2.1.02,15.0.5,14.06,11]icosa-5(14),6,8,10-tetraen-16-one, converting it to sulfide, followed by boiling in the presence of Raney nickel. The resulting compound, 9-methoxy-18,20-dioxapentacyclo-[15.2.1.02,15.0.5, 14.06,11]icosa-5(14),6,8,10,12-pentaenone, is a promising synthetic block for use in the synthesis of estrogen – equilenin. The biological activity of the synthesized compounds was predicted using the PASS computer program, which resulted in the identification of derivatives that are promising for the study of antacid, anti-seborrheic, embryotoxic, and anti-cancer properties.

Medium and large lactones attract the attention of chemists by the uniqueness of their structure, versatile biological activity and limited availability. Among the secondary metabolites of this group, β-lactones are more common, then γ- and δ-lactones, classical and non-classical macrolides, polyene antibiotics, spiro-macrolides and macrolactones. On the basis of many lactones, important preparations of the most diverse pharmacological action have been obtained. Earlier, we proposed a 3-stage scheme for the synthesis of chiral lactones of medium and large size based on levoglucosenone. The lactones obtained according to this scheme contain the carbohydrate residue annelated at the ,γ -positions relative to the hydroxy group. To study the structure-activity relationship, it is necessary to establish the biological role of this carbohydrate residue in reference lactones. For this purpose, a number of lactones were obtained on the basis of levoglucosenone and their in vitro bioscreening of antifungal, antimicrobial, and antitumor activity was performed. It was found that the methyl substituent in the ω-position in the lactone and the benzene ring annulated with the lactone cycle exhibit a slight fungistatic activity towards the fungi: Bipolaris sorokiniana, Fusarium oxysporum, Rhizoctonia solani. Macrocyclic lactone and lactone annelated benzene ring showed weak cytotoxic properties against cells of LOX IMVI (melanoma) and A498, UO-31 (kidney cancer).