Corynantheidine: Chemical And Structural Characterization

Corynantheidine: Chemical & Structural Characterization

Chemical Classification

Corynantheidine is an indolo[2,3-a]quinolizine (Corynanthe-type) plant alkaloid reported from Mitragyna speciosa (kratom) and related Naucleeae taxa.

Data Sources

Core chemical identity and registry information are taken from:

  1. CAS Common Chemistry
  2. NCATS Inxight Drugs
  3. PubChem
  4. ChEBI
Analytical Characterization

Analytical characterization is drawn from peer-reviewed LC–MS/MS method papers and reviews listed in the References.

Identity and Identifiers

Field Value
Preferred name Corynantheidine [1]
CAS Registry Number 23407-35-4 [2]
PubChem CID 3000341 [3]
FDA UNII QMP2RF3L41 [4]
ChEBI ID CHEBI:70073 [5]
EPA CompTox (DSSTox) DTXSID801106946 [6]
InChIKey NMLUOJBSAYAYEM-QALMDFCDSA-N [7]
Synonyms (selected) (–)-Corynantheidine; Isocorynantheidine (stereoisomer);
9-Demethoxymitragynine (catalog synonym)

Composition And Stereochemistry

Property Value
Molecular formula C₂₂H₂₈N₂O₃ [8]
Formula (relative) mass 368.47 g/mol [9]
IUPAC name (one representation) methyl (E)-2-[(2S,3S,12bS)-3-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo
[2,3-a]quinolizin-2-yl]-3-methoxyprop-2-enoate [10]
Stereochemistry 3 defined tetrahedral centers (2S,3S,12bS); one E/Z double bond defined as E [11]

Solid-state and basic physicochemical data

Property Value Notes
Melting point (literature) 152–153 °C free base; when reported [12]
Computed properties XLogP3, tPSA, HBD/HBA, rotatable bonds from “Computed Properties”
panel [13]

Spectroscopic/structural characterization in the literature

Analytical Notes
  1. Peer-reviewed method papers confirm identity/purity using HRMS and (when reported) NMR before quantitative work [14] .
  2. If primary NMR/IR/UV numeric assignments specific to corynantheidine are located in isolation/synthesis papers, include them with solvent/field and cite directly.
  3. If not located, mark “not available in primary literature found.”

Analytical Detection and Quantification

Analytical Methods
  1. Plant/Product QC Panel: UPLC–MS/MS for ten kratom alkaloids (includes corynantheidine). Validated for plant materials and commercial products. Positive-mode ESI, MRM; LLOQ in low ng/mL; run time ~22.5 min to separate all targets [15] .
  2. Single-Analyte Plasma Bioanalysis: UPLC–MS/MS specific to corynantheidine for rat plasma PK: Waters BEH C18 (2.1 × 50 mm), gradient with ammonium acetate (pH 3.5)/acetonitrile; 3.0 min run; ESI+ MRM m/z 369.2→144.0 and 369.2→226.1; linear range 1–500 ng/mL; protein precipitation, 25 µL plasma [16] .
  3. Multi-Analyte Plasma PK: Validated LC–MS/MS for 11 alkaloids in rat plasma applied to kratom tea/liquid shot studies (includes corynantheidine) [17] .

Use-case Matrix Run time Calibration range (ng/mL) Notes
Single-analyte PK Rat plasma 3.0 1–500 MRM 369.2→144.0, 369.2→226.1; 25 µL; protein precipitation
10-analyte QC Leaf/extract/product ~22.5 1–200 (typical) UPLC–MS/MS separation of ten kratom alkaloids
11-analyte PK Rat plasma method-specific validated Applied to oral kratom matrices

Occurrence

Survey and Structural Notes
  1. Minor Component in Surveys: Validated LC–MS/MS surveys report corynantheidine as a minor component (levels vary by material/batch). Use the ten-alkaloid QC method for product-level quantitation; report batch-specific values with method and internal standard details [18] .
  2. Structural Context: Reviews treat corynantheidine as a demethoxy analogue of mitragynine within the same scaffold [19] .

Structure relationships

Structural Analogue
  1. Corynantheidine is the 9-demethoxy analogue of mitragynine within the Corynanthe scaffold; see structural set comparisons in kratom-alkaloid cheminformatics and receptor-binding panels for context (structure only here; no pharmacology) [20] .

Purity assessment, related substances, stability

Standards and QC Notes
  1. Purity / Identity for Standards: Confirm by HRMS (±5 ppm), retention time in a validated LC–MS/MS method, and orthogonal evidence (e.g., NMR) where available [21] .
  2. Related Substances in Plant QC: Monitor co-eluting indole alkaloids per the ten-analyte panel [22] .
  3. Stability: Include only if primary sources report stress-testing or storage data; otherwise, state “no peer-reviewed stability data located.”

Summary

Overview
  1. Corynantheidine (CAS 23407-35-4; C₂₂H₂₈N₂O₃; 368.47 g/mol) is an indolo[2,3-a]quinolizine alkaloid with defined stereochemistry (2S,3S,12bS; E). Identity and registry data are consistent across CAS [23] , Inxight [24] , PubChem [25] , and ChEBI [26] .
  2. Validated UPLC–MS/MS methods exist for plant/product QC [27] , for single-analyte plasma PK with short runtime and documented MRM transitions [28] , and multi-analyte PK assays also include corynantheidine [29] .

References

  1. CAS Common Chemistry. (n.d.). Methyl (αE,2S,3S,12bS)-3-ethyl-1,2,3,4,6,7,12,12b-octahydro-α-(methoxymethylene)indolo[2,3-a]quinolizine-2-acetate (CAS RN: 23407-35-4). CAS.
  2. CAS Common Chemistry. (n.d.). Methyl (αE,2S,3S,12bS)-3-ethyl-1,2,3,4,6,7,12,12b-octahydro-α-(methoxymethylene)indolo[2,3-a]quinolizine-2-acetate (CAS RN: 23407-35-4). CAS.
  3. National Center for Biotechnology Information. (n.d.). PubChem compound summary for CID 3000341: Corynantheidine. PubChem.
  4. National Center for Advancing Translational Sciences. (n.d.). Corynantheidine (UNII: QMP2RF3L41) — Inxight Drugs. NCATS.
  5. European Bioinformatics Institute. (n.d.). ChEBI:70073 — Corynantheidine. EMBL-EBI.
  6. U.S. Environmental Protection Agency. (n.d.). CompTox Chemicals Dashboard — DTXSID801106946 (Corynantheidine). EPA.
  7. CAS Common Chemistry. (n.d.). InChI / InChIKey for CAS 23407-35-4 (NMLUOJBSAYAYEM-QALMDFCDSA-N). CAS.
  8. National Center for Biotechnology Information. (n.d.). PubChem compound summary for CID 3000341: Corynantheidine (formula & properties). PubChem.
  9. National Center for Advancing Translational Sciences. (n.d.). Corynantheidine — Details (molecular weight, stereocenters). NCATS Inxight Drugs.
  10. CAS Common Chemistry. (n.d.). IUPAC/CAS name for CAS 23407-35-4. CAS.
  11. National Center for Advancing Translational Sciences. (n.d.). Corynantheidine — stereochemistry (defined centers/E–Z). NCATS Inxight Drugs.
  12. CAS Common Chemistry. (n.d.). Corynantheidine — melting point (152–153 °C) and identifiers. CAS.
  13. National Center for Biotechnology Information. (n.d.). PubChem compound summary for CID 3000341: Computed properties (XLogP3, tPSA, etc.). PubChem.
  14. King, T. I., Sharma, A., Kamble, S. H., León, F., Berthold, E. C., Popa, R., … Avery, B. A. (2020). Bioanalytical method development and validation of corynantheidine, a kratom alkaloid, using UPLC–MS/MS, and its application to preclinical pharmacokinetic studies. Journal of Pharmaceutical and Biomedical Analysis, 180, 113019. Open access: PMC.
  15. Sharma, A., Kamble, S. H., León, F., Chear, N. J.-Y., King, T. I., Berthold, E. C., … Avery, B. A. (2019). Simultaneous quantification of ten key kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by UPLC–MS/MS. Drug Testing and Analysis, 11(8), 1162–1171. PubMed.
  16. King, T. I., Sharma, A., Kamble, S. H., León, F., Berthold, E. C., Popa, R., … Avery, B. A. (2020). Journal of Pharmaceutical and Biomedical Analysis, 180, 113019. Open access: PMC.
  17. Kamble, S. H., Berthold, E. C., King, T. I., Kanumuri, S. R. R., Popa, R., Herting, J. R., … McCurdy, C. R. (2021). Pharmacokinetics of eleven kratom alkaloids following an oral dose of either traditional or commercial kratom products in rats. Journal of Natural Products, 84(4), 1104–1112. Open access: PMC.
  18. Sharma, A., Kamble, S. H., León, F., … Avery, B. A. (2019). Drug Testing and Analysis, 11(8), 1162–1171. PubMed.
  19. Ellis, C. R., Racz, R., Kruhlak, N. L., Kim, M. T., Zakharov, A. V., Southall, N., … Hawkins, E. G. (2020). Evaluating kratom alkaloids using PHASE. PLOS ONE, 15(3), e0229646. Article.
  20. Ellis, C. R., et al. (2020). Evaluating kratom alkaloids using PHASE — figures/structures. PLOS ONE.
  21. King, T. I., et al. (2020). Journal of Pharmaceutical and Biomedical Analysis, 180, 113019. Open access: PMC.
  22. Sharma, A., et al. (2019). Drug Testing and Analysis, 11(8), 1162–1171. PubMed.
  23. CAS Common Chemistry. (n.d.). CAS RN: 23407-35-4 — Corynantheidine entry. CAS.
  24. National Center for Advancing Translational Sciences. (n.d.). Corynantheidine — Inxight Drugs. NCATS.
  25. National Center for Biotechnology Information. (n.d.). PubChem compound summary for CID 3000341: Corynantheidine. PubChem.
  26. European Bioinformatics Institute. (n.d.). ChEBI:70073 — Corynantheidine. EMBL-EBI.
  27. Sharma, A., et al. (2019). Drug Testing and Analysis, 11(8), 1162–1171. PubMed.
  28. King, T. I., et al. (2020). Journal of Pharmaceutical and Biomedical Analysis, 180, 113019. Open access: PMC.
  29. Kamble, S. H., et al. (2021). Pharmacokinetics of eleven kratom alkaloids following an oral dose of either traditional or commercial kratom products in rats. Journal of Natural Products, 84(4), 1104–1112. Open access: PMC.