Study On The Structural Modification And Asymmetric Catalytic Activity Of C₁₈ Diterpenoid Alkaloids

While chiral alkaloids, as a kind of important natural products, widely exist in the nature, a large of them are unemployed except for using as drugs and chiral catalysts. One aim of our research is to make more chiral alkaloids available in the asymmetric reactions, which provides innovation for the important development of new asymmetric reactions. Furthermore, hydrogen peroxide (H2O2), as a safe and inexpensive oxidant, used in organocatalyzed asymmetric hydroxylation is rare. For the development of new economic and environmentally friendly organic reactions, it is desirable to use hydrogen peroxide as an oxidant in the asymmetric hydroxylation, which is another research object.Forty-six Cis diterpenoid alkaloid derivatives have been synthesized based on the modification of nitrogen-atom and hydroxy, while their catalytic activity for asymmetric α-hydroxylation of β-keto esters has been investigated. The relationship between the structure of diterpenoid alkaloid derivatives and catalytic activity has been systematically studied. The structural modification of hydroxy in C8,9and N(20) made important effect in catalytic activity. The alkaline hydrolysis of ester group in C4or acetalization of hydroxy in C8,9led to increased catalytic activity, but the symmetry of aromatic acetal groups has a directly influence to it. During the screening of β-keto esters with different ester groups, we found that the reactivities of chain alkyl eater> cage alkyl eater> aromatic eater when lappaconitine derivatives as catalysts, but decreased with increasing steric bulk of ester groups when ranaconitine derivatives as catalysts. The electron-withdrawing group in phenyl of β-keto ester made the enantioselective decreased, but electron-donating substituent had an opposite effect. The lappaconitine derivatives had optimal catalytic activity with95%yield and93%ee using TBHP as the oxidant. Using30%H2O2as oxidant, it could shorten reaction time, increase yield, but slightly decrease enantioselective in which lappaconitine derivatives as the catalysts. Interestingly, ranaconitine derivatives could make this enantioselective hydroxylation available only when hydrogen peroxide as the oxidant. This is the first efficient asymmetric α-hydroxylation of β-keto esters by using30%H2O2as the oxidant with up to98%yield and92%ee.The catalytic activity of C18diterpenoid alkaloid derivatives and11familiar chiral natural compounds for asymmetric α-chlorination ofβ-keto esters have been investigated. Besides lappaconitine derivatives, vincamine, vinpocetine and cytisine could also catalyze the reaction, rendering them a class of potential organocatalysts. The secondary amine derivative of lappaconitine has the optimal catalytic activity, afforded the chlorinated products in up to98%yield and68%ee. Based on the experimental data and X-ray single-crystal structure, the postulated transition states for the origin of the stereoselectivity in the asymmetric a-hydroxylation and chlorination processes have been outlined. Finally, the influence of catalysts and the structure of P-keto esters on reactivity has been studied, besides the experimental phenomena.