Studies on the relative reactivity of three hydroxyl groups in aconitine

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-OH13-OH15-OH; (2) 3-OH is much more reactive than 15-OH toward oxidation; and (3) reduction of the carbonyl group at C-3 with NaBH(4) 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-OCH(3). When the substrate has 16β-OCH(3), its carbonyl group at C-15 can be reduced with NaBH(4) to yield exclusively the 15α-OH-containing product. Upon replacement of reducing agent NaBH(4) with LiAlH(4), 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-OCH(3), C-15 carbonyl group can only be reduced to generate 15α-OH-containing product.