Isolation and Structure Elucidation of a Novel Cyclopeptide from Asimina triloba Fruits = Asimina triloba 열매 유래 신규 사이클로펩타이드의 분리 및 구조 규명

다국어 초록 (Multilingual Abstract)

Asimina triloba (pawpaw), a temperate member of the family Annonaceae, has attracted increasing scientific interest due to its diverse secondary metabolites. While acetogenins and other bioactive constituents from the roots, bark, and seeds of A. triloba have been extensively studied, the chemical composition of the fruit remains comparatively unexplored, and no cyclopeptides have been structurally characterized to date. Given the emerging pharmacological significance of plant-derived cyclopeptides-particularly those containing conformationally influential residues such as proline-the discovery of new macrocyclic peptides from underexplored botanical sources remains of considerable interest. In the present study, phytochemical investigation of A. triloba fruit led to the isolation of a previously undescribed cyclic heptapeptide. Its planar structure was elucidated through a comprehensive spectroscopic workflow, including high-field 1H and 13C NMR, as well as 2D NMR experiments (COSY, HSQC, and HMBC), which enabled complete residue identification and established sequential inter-residue connectivities. Long-range HMBC correlations confirmed head-to-tail macrocyclization, while NOESY data provided key spatial proximity constraints supporting the three-dimensional arrangement of the peptide. Electronic circular dichroism (ECD) spectroscopy further contributed to the assessment of the overall chiral topology and supported a well-defined conformational preference of the macrocycle. Collectively, these results establish the complete structure of a new heptacyclopeptide from A. triloba fruit, representing the first cyclopeptide reported from this species. This finding expands the known chemical space of Annonaceae metabolites and highlights A. triloba fruit as a previously overlooked reservoir of structurally and pharmacologically intriguing macrocycles, underscoring its potential value in future natural product discovery and drug development efforts.

목차 (Table of Contents)

• List of Schemes ⅲ
• List of tables ⅲ
• List of Figures ⅲ
• List of Abbreviations ⅴ
• Abstract ⅶ
• Introduction 1
• Materials and Methods 7
• 1. Isolation of constituents from A. triloba fruits 7
• 1.1. Materials 7
• 1.2. Methods 8
• 1.2.1. Extraction and fraction of A. triloba fruits 8
• 1.2.2. Isolation of A. triloba fruits 9
• 1.2.3. HR-TOF-MS Measurement 11
• 1.2.4. ECD Measurement 13
• 1.2.5. TDDFT ECD Calculations 14
• Results and Discussion 15
• 1. Identification of chemical structure of Asiminatide A (3) from A. triloba fruits 15
• 1.1. High-Resolution Mass Spectrometry 15
• 1.2. 1H NMR Spectral Interpretation of Asiminatide A (3) 16
• 1.3. 13C NMR Spectral Interpretation of Asiminatide A (3) 18
• 1.4. COSY Spectral Analysis of the Heptapeptide Backbone 21
• 1.5. HMBC Spectral Analysis of the Heptapeptide Backbone 26
• 1.6. ROESY 31
• 1.7. ECD 31
• 1.8. Assignment of the Proline Amide Geometry 34
• 1.9. Assignment of the two isoleucine residues 34
• 1.10. NMR-based stereochemical analysis of the two Ile residues in Asiminatide A (3)
• 35
• Conclusion 38
• References 40
• 국문초록 47