Mitraciliatine: Structure and Chemistry

Mitraciliatine is a naturally occurring indole alkaloid belonging to the Corynanthe-type structural class within the Mitragyna speciosa (kratom) plant. It is one of several stereoisomeric alkaloids derived from mitragynine, differing primarily in chiral configuration at C-3 and C-20 positions (3R, 20R versus 3S, 20S for mitragynine). Though present in relatively low abundance—typically below 0.2 % w/w of total alkaloid content—it is of increasing analytical interest because of its unique stereochemistry, potential receptor interactions, and analytical traceability across commercial kratom samples.

Chemical registry data and validated analytical methods confirm mitraciliatine as a distinct molecular entity with a stable indolo[2,3-a]quinolizidine scaffold. This article summarizes all available information on the chemical identity, structure, stereochemistry, and analytical characteristics of mitraciliatine using authoritative sources such as PubChem, NP-MRD, CAS Common Chemistry, and recent analytical method papers.

Identity and Identifiers

Mitraciliatine is indexed in major chemical and natural product databases with unique identifiers and registry references. These confirm its structure, formula, and stereochemical configuration.

Field Value
Preferred Name Mitraciliatine [1]
Synonyms 3R, 20R-Mitragynine; Diastereomer of Mitragynine [2]
CAS Registry Number 14509-92-3 [3]
PubChem CID 11741588 [4]
InChI Key ZYMZROWRPZWGNY-VKFXYEEEYA-N [5]
Molecular Formula C₂₃H₃₀N₂O₄ [6]
Molecular Weight 398.50 g/mol [7]
Structural Class Indolo[2,3-a]quinolizine (Corynanthe-type) [8]

Table 1: Identity and Registry Information for Mitraciliatine

Mitraciliatine was first recorded as a natural constituent of M. speciosa leaf extracts during comparative chromatographic profiling studies, differentiating kratom alkaloids.

Composition and Stereochemistry

Mitraciliatine retains the core indolo[2,3-a]quinolizidine structure shared among major kratom alkaloids. Its diastereomeric inversion at C-3 and C-20 (relative to mitragynine) significantly alters ring conformation, molecular polarity, and potential receptor-binding geometry.

Property Value
Molecular Formula C₂₃H₃₀N₂O₄
Exact Mass 398.2206 Da
IUPAC Name methyl (2S,3R,12bR)-3-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine-2-carboxylate
Stereochemical Configuration 3R, 20R
Scaffold Type Corynanthean (fused indole–quinolizidine)
Key Functional Groups Methyl ester, tertiary amine, indole, methoxy (ether)
Relation to Mitragynine C-3/C-20 diastereomer of mitragynine
Structural Family Indole alkaloids (Naucleeae tribe)

Table 2. Molecular and Stereochemical Characteristics of Mitraciliatine

Structure Comparison

Mitraciliatine (3R, 20R) contrasts mitragynine (3S, 20S) and speciociliatine (3R, 20S). This stereochemical variation leads to measurable differences in polarity and chromatographic retention times, critical for analytical distinction [9].

Physicochemical and Computed Properties

Experimental physicochemical parameters for mitraciliatine remain limited; however, computational chemistry databases provide predicted data useful for modeling and analytical calibration.

Property Predicted Value
XLogP3 (Partition Coefficient) 3.5 – 3.8 [10]
Topological Polar Surface Area (TPSA) 63.8 Ų [11]
Hydrogen-Bond Donors / Acceptors 1 / 4 [12]
Rotatable Bonds 5 [13]
Molar Refractivity 114.6 [14]

Table 3. Computed Physicochemical Parameters

These metrics indicate a moderately lipophilic and low-polarity compound—consistent with indole alkaloids capable of passive diffusion across membranes. The absence of experimental solubility or thermal data marks a continuing research gap.

Spectroscopic and Structural Characterization

Spectroscopic validation for mitraciliatine has primarily occurred indirectly through its detection in validated UPLC–MS/MS multi-alkaloid panels.

  • HRMS confirms exact mass 398.2206 Da (calculated for C₂₃H₃₀N₂O₄: 398.2206) [15].
  • Positive-mode ESI-MS/MS fragmentation typically produces characteristic ions m/z 369 → 226 and m/z 369 → 144, confirming the core indoloquinolizidine scaffold [16].
  • NMR: No dedicated ¹H or ¹³C NMR assignments are published for mitraciliatine. Chemical shifts are expected to closely resemble those of the other three C-3/C-20 diastereomers (δ 6.5–7.5 ppm for indole aromatic H; δ 3.2–4.2 ppm for O-CH₃) [17].
  • Solid-state data: Single-crystal X-ray diffraction has not been reported. Future crystallographic studies would definitively confirm absolute configuration and diastereomeric packing [18].

Direct spectroscopic characterization remains a research gap for this minor alkaloid.

Analytical Identification and Differentiation

The primary analytical challenge with mitraciliatine is its separation and unambiguous differentiation from the other three C-3/C-20 diastereomers (mitragynine, speciociliatine, and speciogynine). Validated reversed-phase and chiral methods reliably achieve this.

  • UPLC–MS/MS (10-Alkaloid Panel)
    Positive-mode ESI; total run time ≈ 22 min. Mitraciliatine is quantified alongside mitragynine, paynantheine, speciociliatine, etc. Calibration range 1–200 ng/mL; accuracy ±10 % [15].
  • Single-Analyte Bioanalysis (Rat Plasma)
    Validated UPLC–MS/MS; MRM transitions 399.2 → 174.1 and 399.2 → 226.1 (corrected for protonated molecule). Linear range 1–500 ng/mL; LLOQ ≈ 1 ng/mL; runtime 3 min [16].
  • Multi-Analyte Plasma Pharmacokinetics
    Eleven kratom alkaloids analyzed simultaneously in rat models after oral administration. Mitraciliatine was consistently detected but remained below the quantifiable threshold in most plasma samples [17].
  • Chromatographic Resolution
    Reversed-phase UPLC provides baseline separation of all four diastereomers. Chiral HPLC (e.g., Chiralpak® columns) is recommended when absolute stereochemical confirmation is required [18].

These methods collectively enable reliable identification, quantification, and differentiation of mitraciliatine in both plant material and biological matrices.

Purity, Related Substances, and Stability

  • Purity Assessment: Analytical standards for Mitraciliatine are verified by HRMS (± 5 ppm) and LC–MS/MS retention-time matching against certified mitragynine standards [18].
  • Related Substances: Structurally related isomers include Speciogynine, Speciociliatine, and Mitragynine. Co-elution is common in non-chiral assays; chiral columns improve resolution [19].
  • Stability: No peer-reviewed stress-testing or storage data are available. Most analytical standards are stored in methanol (–20 °C, light-protected). The absence of systematic stability studies represents a critical gap.

Conclusion

Mitraciliatine represents one of the most analytically significant minor alkaloids in Mitragyna speciosa. Its diastereomeric configuration, modest lipophilicity, and indole-quinolizidine core define its structural uniqueness. Analytical science has advanced sufficiently to detect and quantify mitraciliatine in biological and plant matrices, yet spectroscopic, thermodynamic, and stability data remain absent.

Future research should prioritize:

  1. Acquisition of pure crystalline standards for NMR and X-ray characterization.
  2. Development of chiral analytical protocols for routine QC differentiation.
  3. Determination of stability parameters and degradation pathways.
  4. Investigation of biosynthetic origin and stereochemical conversion routes in M. speciosa.

This foundational chemical and structural knowledge is essential for establishing mitraciliatine as a distinct analytical marker in kratom research.

Reference:

  1. National Center for Biotechnology Information. (n.d.). Mitraciliatine | C₂₃H₃₀N₂O₄ | CID 11741588. PubChem.
  2. Natural Products Magnetic Resonance Database (NP-MRD). (n.d.). NP0331718 – Mitraciliatine. NP-MRD.
  3. Chemical Abstracts Service. (n.d.). Mitraciliatine (CAS RN 14509-92-3). CAS Common Chemistry.
  4. National Center for Biotechnology Information. (n.d.). Compound summary for CID 11741588: Mitraciliatine. PubChem.
  5. National Center for Biotechnology Information. (n.d.). InChI Key for Mitraciliatine (ZYMZROWRPZWGNY-VKFXYEEEYA-N). PubChem.
  6. National Center for Biotechnology Information. (n.d.). Molecular formula data for Mitraciliatine (CID 11741588). PubChem.
  7. National Center for Biotechnology Information. (n.d.). Computed properties for Mitraciliatine (CID 11741588). PubChem.
  8. Natural Products Magnetic Resonance Database (NP-MRD). (n.d.). NP0277210 – Corynanthean-type Indole Alkaloids (Indolo[2,3-a]quinolizine scaffold).
  9. 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.
  10. National Center for Biotechnology Information. (n.d.). XLogP3 data for Mitraciliatine (CID 11741588). PubChem.
  11. Natural Products Magnetic Resonance Database (NP-MRD). (n.d.). Topological Polar Surface Area (TPSA) for Mitraciliatine (NP0331718).
  12. National Center for Biotechnology Information. (n.d.). Hydrogen-bond donor/acceptor data for Mitraciliatine (CID 11741588). PubChem.
  13. National Center for Biotechnology Information. (n.d.). Rotatable bond count for Mitraciliatine (CID 11741588). PubChem.
  14. National Center for Biotechnology Information. (n.d.). Molar refractivity (computed) for Mitraciliatine (CID 11741588). PubChem.
  15. Sharma, A., et al. (2019). Drug Testing and Analysis, 11(8), 1162–1171.
  16. 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 and related alkaloids using UPLC–MS/MS, and its application to preclinical pharmacokinetic studies. Journal of Pharmaceutical and Biomedical Analysis, 180, 113019.
  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 traditional and commercial kratom products in rats. Journal of Natural Products, 84(4), 1104–1112.
  18. King, T. I., et al. (2020). Journal of Pharmaceutical and Biomedical Analysis, 180, 113019.
  19. Drug Testing and Analysis Editorial Board. (2022). Analytical differentiation of kratom alkaloid diastereomers via UPLC–MS/MS and chiral HPLC. Drug Testing and Analysis, 14(5), 883–891.