O-Methylarmepavine
[CAS# 5701-00-8]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Isoquinoline compound
• Name: O-Methylarmepavine
• Synonyms: (1R)-6,7-dimethoxy-1-[(4-methoxyphenyl)methyl]-2-methyl-3,4-dihydro-1H-isoquinoline
• Molecular Formula: C₂₀H₂₅NO₃
• Molecular Weight: 327.42
• CAS Registry Number: 5701-00-8
• SMILES: CN1CCC2=CC(=C(C=C2[C@H]1CC3=CC=C(C=C3)OC)OC)OC

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 445.7±45.0 ºC 760 mmHg (Calc.)^*
• Flash point: 126.9±25.9 ºC (Calc.)^*
• Index of refraction: 1.558 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

O‑Methylarmepavine is a benzyl‑tetrahydroisoquinoline alkaloid with molecular formula C₂₀H₂₅NO₃. It contains a 6,7‑dimethoxy‑1‑(4‑methoxybenzyl)‑2‑methyl‑1,2,3,4‑tetrahydroisoquinoline scaffold. This naturally occurring compound is primarily isolated from the twigs of Annona squamosa and other species of the Annonaceae family. Its structure includes two methoxy substituents on the isoquinoline ring, a methylated nitrogen, and a 4‑methoxybenzyl moiety, which contribute to both its chemical reactivity and biological activity.

The discovery of O‑Methylarmepavine originated from phytochemical investigations aimed at identifying bioactive benzylisoquinoline alkaloids. Standard extraction techniques, including acid-base partitioning and chromatographic separation, were employed to isolate the compound from plant material. Its structure was elucidated using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), confirming the configuration and positions of the substituents.

O‑Methylarmepavine exhibits notable pharmacological properties. It has been found to inhibit H⁺/K⁺-ATPase activity, suggesting potential anti-ulcer effects. In addition, it demonstrates leishmanicidal activity against both promastigote and amastigote forms of Leishmania species, and in animal models, it modulates immune responses. Its bioactivity makes it a candidate for further research in natural product pharmacology.

The compound also serves as a valuable intermediate for chemical derivatization. Its methoxy groups and benzyl side chain allow for selective transformations such as demethylation, further methylation, or substitution reactions, which can be applied to generate analogues with modified biological properties. The stereochemistry of the tetrahydroisoquinoline core is critical for biological activity, and synthetic or isolation methods aim to preserve the S‑configuration where relevant.

Handling and storage of O‑Methylarmepavine follow standard laboratory precautions for alkaloids. It is typically stored in a cool, dry environment protected from light to maintain stability. Extraction and purification require careful manipulation of organic solvents, pH adjustments, and chromatographic techniques to achieve high purity for biological studies.

O‑Methylarmepavine continues to be of interest in phytochemistry, medicinal chemistry, and pharmacological research due to its chemical versatility and biological activity. It is used as a reference compound in studies of benzylisoquinoline alkaloids and as a scaffold for designing derivatives with potential therapeutic applications.

References

Sun L, Zhu H, Gan L, Mo J, Feng F, Zhou C (1992) Studies on the chemical constituents of Annona squamosa. Zhongguo Zhong Yao Za Zhi 17, 112–115. PMID: 1414383

Al‑Ghazzawi AM, Al‑Shalabi EM, Al‑Tawaha AR (2019) Anti‑cancer activity of a benzyl‑isoquinoline alkaloid from Annona squamosa. BMC Chemistry 13, 13. DOI: 10.1186/s13065-019-0536-4