Introduction
Mitragynine (1) is a major alkaloidal component in the Thai traditional medicinal herb, Mitragyna speciosa, and has been proven to exhibit analgesic activity mediated by opioid receptors. The oxidative derivatives of mitragynine, i.e., mitragynine pseudoindoxyl (4) and 7-hydroxymitragynine (3), were found as opioid agonists with higher potency than morphine. Mitragynine pseudoindoxyl (2) may be obtained from Mitragynine (1) by three steps. Mitragynine (1) may be obtained by Kratom Acid-Base Extraction from Kratom leafs.
Equipment and glassware:
- 10 and 100 mL pear shaped flasks;
- Magnetic stirrer with heater;
- Retort stand and clamp for securing apparatus;
- 100 mL x3; 50 mL x3 Beakers;
- Glass rod and spatula;
- Nitrogen ballon ~5 L (1 bar);
- Ice;
- 500 mL Separatory funnel;
- Flash chromatography kit;
- Rotovap machine;
- Vacuum desiccator;
- Reflux condenser.
Reagents:
- Mitragynine (1) (105 mg, 0.26 mmol);
- Dichloromethane (CH2Cl2) ~114 mL;
- Lead(IV) acetate (Pb(OAc)4) 259 mg, 91% purity, 0.53 mmol;
- Argon or nitrogen balloon ~10 L (1 bar);
- Magnesium sulphate (MgSO4) ~100 g;
- Sodium sulphate (NaOH) 0.3 mL 15% aq solution;
- Methanol (MeOH) 8 mL [dry];
- Chloroform (CHCl3) ~150 mL;
- Sodium chloride ~50g;
- Hexane ~120 mL;
- AcOEt ~80 mL;
- Sodium methylate (NaOMe) 19 mg, 0.35 mmol.
Boiling Point: 580.9±50.0 °C at 760 mm Hg;
Melting Point: 170 - 172 °C;
Molecular Weight: 414.502 g/mole;
Density: 1.2±0.1 g/mL;
CAS Number: N/A.
Procedure
7-acetoxyindolenine derivative (2)To a stirred solution of Mitragynine (1) (105 mg, 0.26 mmol) in dry CH2Cl2 (14 mL) was added Pb(OAc)4 (259 mg, 91% purity, 0.53 mmol) at 0 °C under argon or nitrogen atmosphere in 100 mL pear shaped flask. After the reaction mixture was stirred for 1.5 h, the reaction mixture was poured onto the chilled water and was extracted with CH2Cl2 five times. The combined organic layer was washed with brine, dried over MgSO4, and evaporated. The residue was separated by Al2O3 column chromatography (Woelm N, grade III, CH2Cl2) to give (2) (60 mg, 50 %) as a yellowish amorphous powder.
7-hydroxy-7H-mitragynine (3)
A mixture of (2) (70 mg, 0.16 mmol) and aqueous 15% NaOH (0.3 mL) in MeOH (2 mL) was stirred at 0 °C under inert atmosphere for 2 h. The reaction mixture was poured onto the chilled water and was extracted with CHCl3 five times. The combined organic layer was washed with brine, dried over MgSO4, and evaporated. The residue was separated by Al2O3 column chromatography (n-hexane/AcOEt 6:4) to give (3) (62 mg, 95 %) as an amorphous powder.
Mitragynine pseudoindoxyl (4)
A solution of (3) (66 mg, 0.16 mmol) and NaOMe (19 mg, 0.35 mmol) in dry MeOH (6 mL) was heated under reflux for 12 h under argon atmosphere. The reaction mixture was cooled, poured onto the chilled water, and then extracted with CHCl3 three times. The combined organic layer was washed with brine, dried over MgSO4, and evaporated. The residue was separated by SiO2 column chromatography (n-hexane/AcOEt 1:2) to give (4) (32 mg, 48 %) as an amorphous powder.
A solution of (3) (66 mg, 0.16 mmol) and NaOMe (19 mg, 0.35 mmol) in dry MeOH (6 mL) was heated under reflux for 12 h under argon atmosphere. The reaction mixture was cooled, poured onto the chilled water, and then extracted with CHCl3 three times. The combined organic layer was washed with brine, dried over MgSO4, and evaporated. The residue was separated by SiO2 column chromatography (n-hexane/AcOEt 1:2) to give (4) (32 mg, 48 %) as an amorphous powder.
Last edited by a moderator:
