Tatyana S. Khlebnicova

Synthesis of novel lupane triterpenoid-indazolone hybrids with oxime ester linkage.

Graphical abstract Figure. No Caption available. HighlightsNovel lupane triterpenoid‐indazolone hybrids with oxime linkage are obtained.This is the first report on oxime esters derived from betulonic and betulinic acid at their C(28).X‐ray structure of the hybrid molecule is reported.Purification procedure for betulonic acid via its cyclohexylammonium salt is developed. Abstract An efficient protocol for the synthesis of novel lupane triterpenoid‐indazolone hybrids with oxime ester linkage has been developed from naturally accessible precursor betulin. For the first time a series of betulonic acid‐indazolone hybrids have been synthesized via an acylation of corresponding 6,7‐dihydro‐1H‐indazol‐4(5H)‐one oximes with betulonic acid chloride. Diastereoselective reduction of the obtained betulonic acid conjugates with NaBH4 resulted in a formation of betulinic acid‐indazolone hybrids in excellent yields. The configuration of the key compounds has been fully established by X‐ray and 2D NMR analysis.

Fluorine-containing lupane triterpenoid acid derivatives: Design, synthesis and biological evaluation as potential anti-inflammatory agents

&NA; A series of novel fluorine‐containing lupane triterpenoid acid derivatives with fluoroaromatic amide moieties at the C‐28 position (1–8) or with 2‐(fluoroacyl)cyclopentane‐1,3‐dione fragments at the C‐3 position (9–18) of lupane skeleton was synthesized. A simple synthesis of novel lupane triterpenoid hybrids with 2‐(fluoroacyl)‐2‐cyclopenten‐1‐one moieties was developed. An interaction of 2‐acyl‐3‐chlorocyclopent‐2‐en‐1‐ones, obtained from corresponding cyclic &bgr;‐triketones, with methyl 3‐amino‐3‐deoxybetulinate gave 3&bgr;‐isomers (9–13) and 3&agr;‐isomers (14–18) of target hybrids, which were isolated as individual compounds. Anti‐inflammatory properties of selected synthesized compounds were studied in vivo using the histamine‐, concanavalin A‐ and sheep erythrocytes immunization‐induced mouse paw edema models. The antioxidant activity was investigated in vivo on the model of tetracycline‐induced hepatitis. Majority of synthesized fluorine‐containing lupane triterpenoid acid derivatives exhibited significant anti‐inflammatory and antioxidant effects. Among studied compounds, 3&bgr;‐hybrid 11 with 2‐perfluorobutanoyl‐2‐cyclopenten‐1‐one moiety was the most potent bioactive compound.