Efficient synthesis of (R)-harmonine--the toxic principle of the multicolored Asian lady beetle (Harmonia axyridis).

Abstract

A flexible synthetic route to (R)-harmonine ((R)-1), the toxic principle of the Asian lady beetle Harmonia axyridis (H. axyridis), via reductive olefination of the macrocyclic lactone (S)-5, is reported. High enantiomeric purity is achieved by enantioselective saponification of the lactone rac-5 with horse liver esterase. Minor modifications in the synthetic route give access to racemic and chiral harmonine ()1, analogs and putative biosynthetic precursors. In addition, the antimicrobial activity of harmonine against Leishmania major (L. major) is demonstrated and provides the rationale for harmonine-based drug development against parasitic diseases.

• Authors: Nadja C Nagel, Anita Masic, Uta Schurigt, Wilhelm Boland
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 13 Issue 18 Pg. 5139-46 (May 14 2015) ISSN: 1477-0539 [Electronic] England
• PMID: 25835581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkenes
• Anti-Infective Agents
• harmonine

Topics

• Alkenes (chemical synthesis, chemistry, pharmacology, toxicity)
• Animals
• Anti-Infective Agents (chemical synthesis, pharmacology)
• Carbon-13 Magnetic Resonance Spectroscopy
• Coleoptera
• Hydrogen-Ion Concentration
• Mass Spectrometry
• Proton Magnetic Resonance Spectroscopy
• Stereoisomerism