源于原人参二醇的ocotillol型C24差向异构体的形成机理探讨

Formation Mechanism of C24 Epimeric Ocotillol-Type Ginsenosides Driven from 20(S)-and 20(R)-Protopanaxadiol

C24差向异构ocotillol型人参皂苷的心肌保护作用及其药代动力学性质存在显著立体差异,有关其半合成的研究已有报道,但其形成机理研究报道较少.20(S/R)-原人参二醇经过氧酸氧化得到C24差向异构ocotillol型皂苷,结合烯烃双键的环氧化反应和亲核取代反应特点,推测其形成机理为:过氧酸从烯烃平面两侧氧化24(25)碳碳双键,生成C24差向异构24,25-环氧中间体,在酸性条件下,该环氧中间体氧原子接受一个质子,生成徉盐,20位羟基氧原子进攻24位碳原子,经分子内S_N2反应,生成C24差向异构体.

There are significant stereoselectivity differences in myocardial protection and ADME for the C24 epimers of ocotillol-type ginsenosides. In recent years,there are reports on the semi-synthesis of the C24 epimers of ocotillol-type ginsenosides,but the formation mechanism is rarely reported. The C24 epimers of ocotillol-type ginsenosides are synthesized from 20（ S）-protopanaxadiol and 20（ R）-protopanaxadiol. On the basis of the previous research results,by combining the characteristics of epoxidation reaction of olefins double bond and nucleophilic substitution,the formation mechanism of C24 epimers is inferred. C24（ 25） double bond is oxidized by m-CPBA from both sides of the plane,generating C24 epimers of 24,25-epoxy intermediates. Under acidic conditions,the oxoniumsalt is generated by the oxygen atoms of epoxy intermediate that accept a proton. The 24-carbon atom is attacked by the oxygen atom of 20-hydroxyl,then C24 epimers are prepared by the intramolecular S_N2 reaction.