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EXPERIMENTAL AND QUANTUM-CHEMICAL STUDY OF NUCLEOPHILIC SUBSTITUTION MECHANISM IN BERBERINE

Олег Н. Буров, Михаил Е. Клецкий, Никита С. Федик, Сергей В. Курбатов, Антон В. Лисовин
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Abstract


Principal differences in the interaction mechanisms of alkaloid berberine with primary and secondary amines were investigated experimentally and by quantum-chemical calculations according to density functional theory (DFT/B3LYP) with 6-31G** basis set. The nucleophilic substitution of 9-metoxy group with primary amine was shown to proceed through a stage of σ-complex formation and led to 9-alkylamino derivatives of berberine. Analogous substitution with a secondary amine did not occur due to unfavorable thermodynamic parameters. The secondary amine participated in this reaction not as the attacking nucleophile, but rather as a bifunctional catalyst of berberine hydrolysis to berberrubine. The driving force for all these rocesses was the stabilization of products by hydrogen bonding. Based on the obtained results, we developed a new effective method for the preparation of berberrubine, one of the key intermediates in synthetic transformations of berberine. New 9-monoalkylamino derivatives of berberine containing indole moieties were synthesized.

How to Cite
Burov, O. N.; Kletskii, M. E.; Fedik, N. S.; Kurbatov, S. V.; Lisovin, A. V. Chem. Heterocycl. Compd. 2015, 51, 997. [Khim. Geterotsikl. Soedin. 2015, 51, 997.]

For this article in the English edition see DOI 10.1007/s10593-016-1810-1


Keywords


berberine; berberrubine; alkylamination; catalytic hydrolysis; DFT calculations

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