Novel lupane triterpenoids containing allyl substituents in ring A: synthesis and in vitro study of antiinflammatory and cytotoxic properties

Abstract

Selective methods for the synthesis of C(2)-monoallyl and C(2)-diallyl derivatives of lupane terpenoids were developed. The methods involve reactions of allyl halides with potassium enolates or potassium enoxy(triethyl)borates generated in situ from 3-oxolupanes (betulonic acid, 3-oxo betulin) under the action of KN(SiMe3)2, KH, or ButOK with subsequent addition of Et3B. The use of the reagent KN(SiMe3)2-Et3B in 1,2-dimethoxyethane ensured the kinetically controlled generation of enolate anions, which yielded 2β-propenyl lupane terpenoids with high stereoselectivity. Reactions of 3-oxolupanes with excesses of ButOK and allyl halide (2.5 equiv.) gave 2,2-bisallylation products. In vitro studies revealed that one of the latter efficiently suppresses the NO production by activated macrophages and has an antitumor effect on Ehrlich carcinoma and P-815 mastocytoma cell lines.