Studies on the relative reactivity of three hydroxyl groups in aconitine

Abstract

The relative reactivity of three hydroxyl groups in aconitine toward acetylation, chlorination, sulfonylation, and oxidation has been studied in this paper. The reduction of C-3 ketone and C-15 ketone derivatives of aconitine was also investigated. It was found that (1) the relative reactivity of three hydroxyl groups toward acetylation, chlorination, and sulfonylation is 3-OH>13-OH>>15-OH; (2) 3-OH is much more reactive than 15-OH toward oxidation; and (3) reduction of the carbonyl group at C-3 with NaBH₄ generated a pair of C-3 epimers, while the reduction products of the carbonyl group at C-15 depend largely on the specific reducing agent and the absolute configuration of 16-OCH₃. When the substrate has 16β-OCH₃, its carbonyl group at C-15 can be reduced with NaBH₄ to yield exclusively the 15α-OH-containing product. Upon replacement of reducing agent NaBH₄ with LiAlH₄, the C-15 carbonyl group can be reduced to yield a pair of C-15 epimers. On the other hand, when the substrate has 16α-OCH₃, C-15 carbonyl group can only be reduced to generate 15α-OH-containing product.

Keywords:

• aconitine
• regioselective reaction
• oxidation
• chlorination
• sulfonation

Acknowledgments

We are grateful to the National Natural Science Foundation of China (No. 81072550) for financial support of this research.