The Synthesis of Methoxymethyl Derivatives of Boldine: Versatile Protected Precursors of Substituted Boldine Derivatives

Abstract

Two new versatile protected precursors of substituted boldine (1) derivatives have been synthesized, isolated, and fully characterized: 9‐O‐methoxymethylboldine (5) and 2,9‐O,O′‐dimethoxymethylboldine (6). There was no evidence of the presence of 2‐O‐methoxymethylboldine (7) in the reaction mixture. These compounds are expected to exhibit an ortho‐directing capacity for further aromatic substitution, which constitutes an attractive alternative to the electrophilic substitution of unprotected boldine, as the methoxymethyl group can be easily removed under mild conditions.

Keywords:

• Aromatic substitution
• boldine derivatives
• synthesis

Acknowledgments

The authors are grateful to the Universidad Técnica Federico Santa María (Proy. D.G.I.P. 13.02.02) for financial support. We thank Professor Bruce Cassels (Universidad de Chile) for some helpful comments.