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

作者：Spivak A Yu^*; Shakurova E R; Nedopekina D A; Khalitova R R; Khalilov L M; Odinokov V N; Bel'skii Yu P; Ivanova A N; Bel'skaya N V; Danilets M G; Ligacheva A A

来源：Russian Chemical Bulletin, 2011, 60(4): 694-701.

DOI：10.1007/s11172-011-0108-9

• pentacyclic lupane triterpenoids
• ketone enolates
• kinetic and thermodynamic control
• allylic alkylation
• nitrogen monoxide
• activated macrophages
• antiinflammatory activity
• antitumor activity

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(SiMe(3))(2), KH, or Bu(t)OK with subsequent addition of Et(3)B. The use of the reagent KN(SiMe(3))(2)-Et(3)B in 1,2-dimethoxyethane ensured the kinetically controlled generation of enolate anions, which yielded 2 beta-propenyl lupane terpenoids with high stereoselectivity. Reactions of 3-oxolupanes with excesses of Bu(t)OK 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.

• 出版日期2011-4