7OH MItragynine
Lab Notes
Required Solvents (extraction isolation)
Chloroform - make from acetone and bleach
Petroleum ether (not actually an ether by any chemical means)- (consists of mostly hexanes and Pentanes), byuproduct of fuel production, carries an entourage of aliphatic hydrocarbons- Buying online somewhere...Serves as a defatting agent -
Not necessary but for clarification purposes*** Diethyl ether - derivable from starter fluid when separated into diethyl ether and hexane. A single petroleum will be used, hexane, due to its availability. Hexane will be separated from john deere starter fluid (~20% hexane)
Required solvents/reagents for conversion
Oxone - relatively cheap
NaHCO3 - derp
Acetone - easily buy
EtOAc- ethyl acetate - can make from combination of alcohol and glacial acetic acid (GAA made from vinegar OR sulfuric acid with sodium acetate) with strong acid catalyst
tri ethyl amine - easily purchasable
Extraction and isolation of mitragynine
Below is presented the scheme from Mohamad Razak et al.
This is the original scheme and will be corrected for the use of 2L of solvent everything down by half
Fresh Mitragyna speciosa Korth leaves (1.0 kg) were washed with water to remove dirt and adhering material, oven dried at 45-50 °C for three days and milled into fine powder using a blender to get the dry powder (297.0 g). Soxhlet extraction was carried out using 297.0 g powdered leaves with 4 L petroleum ether (40-60 oC) for 8 hour, then petroleum ether solution was discarded and the defatted powdered leaves were dried and the extraction was repeated with 4 L chloroform for 8 hour. The chloroform solution obtained was filtered, concentrated, evaporated to dryness under the reduced pressure using rotary evaporator and was kept in a refrigerator (-200C). The dried crude chloroform extract was subjected for flash chromatography according to the method of Still et al.[10]. Crude fraction containing mitragynine was obtained by eluting with hexane and ethyl acetate (80:20 v/v) and this fraction (100 mL) was subjected to liquid-liquid fractionation using petroleum ether (100 mL X 3 times) for further purification. The petroleum ether layer was discarded and the remaining solution was concentrated under the reduced pressure using a Buchi R215 Rotavapor (Flawil, Switzerland) to obtain crude mitragynine.
Corrected scheme
148.5 g of starting material is soxhlet extracted for 8 hours, first in 2L of petroleum ether, then in 2L of chloroform. Ether solution is discarded and the chloroform fraction is rotovapped to dryness, the chloroform is reclaimed and crude extract isolated. Dried crude chloroform extract was subjected to flash chromatography according to Still et al. (general procedure below).
Chromatography fraction was obtained from the Crude fraction using 80:20 V/V and this 100mL fraction was subjected to liquid liquid extraction using 100mL petroleum ether 3 times for further purification via a separatory funnel. Discard pet. ether and concentrate remaining solution under roto-vap to obtain crude mitragynine.
Purification by recrystallization will not be sought in this exp.
Mitragynine to 7-OH Conversion Method
7-Hydroxymitragynine: Oxone Oxidation
To a solution of mitragynine (199 mg, 0.500 mmol) in acetone (15 mL), was added saturated aqueous NaHCO 3 (10 mL), and the mixture was cooled to 0 °C. A solution of Oxone monopersulfate (2KHSO 5 · KHSO 4 · K2 SO4 , MW = 615.5; 308 mg, 0.500 mmol) in water (5 mL) was then added dropwise over 25 minutes and the mixture left to stir at 0 °C for an additional 15 minutes. At this time, the reaction was diluted with water (60 mL) and extracted with EtOAc (3 x 30 mL). The combined organics were washed with brine (30 mL), dried over Na2 SO4 , and concentrated in vacuo to give the crude product as a pale-orange foam (170 mg). This material was purified by column chromatography (6:4 hexanes:EtOAc + 2% Et3 N) to provide pure 7-hydroxymitragynine as an amorphous, pale-yellow solid (115 mg, 55%). Spectral and physical properties were in agreement with those previously reported.1
It is worth nothing, room temp exposure to oxygen and UV light also performs this reaction, albeit to a much lower yield, ~8%.
Source:
Supporting information containing exact methods
Flash Chromatography. General Procedure via Stil et al.
Flash Chromatography. General Procedure. First a low viscosity solvent system (e.g., ethyl acetateh0-60 "C petroleum etherla is found which separates the mixture and moves the desired component on analytical TLC to an Rf of 0.35.9If several compounds are to be separated which run very close on TLC, adjust the solvent to put the midpoint between the components at Rf = 0.35. If the compounds are widely separated, adjust the R, of the less mobile component to
0.35. Having chosen the solvent, a column of the appropriate diameter (see text, Table I) is selected and a small plug of glass wool is placed in the tube connecting the stopcock to the column body (A in the diagram above). Two telescoping lengths of glass tubing (6and 8 mm
0.d.) make placement of the glass wool plug easy. Next a smooth '/a in. layer of 50-100 mesh sand is added to cover the bottom of the column and dry 40-63 pm silica gel is poured into the column in a single portion to give a depth of 5.5-6 in. With the stopcock open, the column is gently tapped vertically on the bench top to pack the gel. Next a l/a in. layer of sand is carefully placed on the flat top of the dry gel bed and the column is clamped for pressure packing and elution. The solvent chosen above is then poured carefully over the sand to fill the column completely. The needle valve (B) of the flow controller is opened all the way and the flow controller is fitted tightly to the top of the column and secured with strong rubber bands. The main air line valve leading to the flow controller is opened slightly and a finger is placed fairly tightly over the bleed port (C). This will cause the pressure above the adsorbent bed to climb rapidly and compress the silica gel as solvent is rapidly forced through the column. It is important to maintain the pressure until all the air is expelled and the lower part of the column is cool; otherwise, the column will fragment and should be repacked unless the separation desired is a trivial one. Particular care is necessary with large diameter columns. The pressure is then released and excess eluant is forced out of the column above the adsorbent bed by partially blocking the bleed port (C). The top of the silica gel should not be allowed to run dry. Next the sample is applied by pipette as a 20-250% solution in the eluant to the top of the adsorbent bed and the flow controller is briefly placed on top of the column to push all of the sample into the silica gel." The solvent used to pack the column is ordinarily reused to elute the column. The walls of the column are washed down with a few milliliters of fresh eluant, the washings are pushed into the gel as before, and the column is carefully filled with eluant so as not to disturb the adsorbent bed. The flow controller is finally secured to the column and adjusted to cause the surface of the solvent in the column to fall 2.0 in./min. This seems to be an optimum value of the flow rate for most low viscosity solvents for any column diameter with the 40-63 km silica gel. Fractions are
collected until all the solvent has been used (see Table I to estimate the amount of solvent and fraction size). It is best not to let the column run dry since further elution is occasionally necessary. Purified components are identified as described in the text by TLC. If the foregoing instructions are followed exactly, there is little opportunity for the separation to fail.
Although we generally pack fresh columns for each separation,the expense of large-scale separations makes it advantageous to reuse large diameter columns. Column recycling is effected by first flushing (rate = 2 in./min) the column with approximately 5 in. of the more polar component in the eluant (generally ethyl acetate or acetone) and then with 5 in. of the desired eluant. If the eluant is relatively nonpolar (e.g., 110% EtOAc/petroleum ether), it may be more advisable to use a flushing solvent (e.g., 2040% EtOAc/petroleum ether) which is somewhat less polar than the pure high polarity component.
Older less effective isolation technique described here, just for comparative purposes
Isolation of Mitragyna speciosa Alkaloids. Dry, finely powdered Mitragyna speciosaleaves (186 g) (Thai strain, Arena Ethnobotanicals, Del Mar, CA) were extracted repeatedly withboiling MeOH (4 x 500 mL), vacuum filtering the solids thoroughly between each extraction.The combined extracts were concentrated to provide a dark green-black solid (56.19 g). Thismaterial was crushed and extracted twice with room temperature 10% aqueous AcOH (2 x 300mL), filtering each extract through celite (slow). The combined, coffee-colored acidic extracts,were washed with hexanes (2 x 150 mL) and carefully basified (with ice cooling) to pH 8-9using concentrated aqueous NaOH (thick tan precipitate forms). The basic mixture was thenextracted thoroughly with CHCl3 (6 x 200 mL, emulsions), shaking vigorously with eachextraction (not all solids dissolve). The combined organics were washed with water (2 x 400mL), dried over Na2SO4, and concentrated to yield the crude alkaloid fraction as a foamy brownsolid (3.62 g, 1.9 mass%). TLC analysis of this material revealed four distinct spots(mitragynine, paynantheine, speciogynine, and speciociliatine in order of increasing polarity), inaddition to baseline. The crude alkaloid mixture was separated by column chromatography (8:2→ 7:3 → 6:4 → 1:1 hexanes:EtOAc + 2% Et3N, 2 column volumes each) to provide fractionscontaining pure mitragynine (1.38 g), mitragynine + minor paynantheine and speciogynine (0.25g), paynantheine and speciogynine + minor mitragynine and speciociliatine (0.61 g),speciociliatine + minor paynantheine and speciogynine (0.20 g), and speciociliatine + minorimpurities (0.20 g). These mixed fractions were further separated by repeated columnchromatography (gradients of hexanes:EtOAc mixtures, with or without 2% Et3N) to provideadditional mitragynine (190 mg), along with pure samples of paynantheine (46 mg),speciogynine (12 mg), and speciociliatine (148 mg). The total yield of isolated mitragynine was1.57 g (0.84 mass%), and of total mixed paynantheine, speciogynine, and speciocoliatine was S191.01 g (0.54 mass%). However, the yields for the pure samples of the minor alkaloids should notbe considered indicative of the quantities contained in the plant material, due to purificationlosses.This isolation procedure was repeated a second time on a larger, separate batch ofpowdered Mitragyna speciosa leaves (454 g), scaling quantities appropriately. It should be notedthat in this second extraction, it was found that basification of the aqueous extracts to pH 12(instead of 8-9) was beneficial, as it prevented the formation of emulsions in the subsequentCHCl3 extractions. This extraction provided the crude alkaloid fraction as a foamy, greenishbrown solid (8.03 g, 1.8 mass%). The mixed alkaloids were separated by columnchromatography as before, to provide pure mitragynine (3.33 g, 0.73 mass%) and fractionscontaining mixtures of the minor alkaloids (total >3 g). No effort was made to further purifypaynantheine, speciogynine, and speciociliatine from the mixed fractions, but the ratios betweenthese alkaloids clearly differed from the first extraction, with speciociliatine being significantlymore prevalent. Mitragynine. Isolated as an amorphous, pale-yellow solid.
Previous Oxidation/conversion techniques reported...
Mitragynine was easily oxidized to 7-hydroxymitragynine (7-OH) by the literature procedure1 employing the hypervalent iodinespecies [bis(trifluoroacetoxy)iodo]benzene (PIFA), but this reaction produced numerousbyproducts and was low yielding. It was also found that the same transformation could beperformed cleanly using singlet oxygen generated by irradiation with visible light in the presenceof rose bengal, under air or pure O2 atmosphere, but yields were still modest (Scheme S1A).Interestingly, it was also found that this photooxidation reaction could take place at roomtemperature under sunlight illumination, with no need for the addition of an external reducingagent, albeit in low yield (8% by NMR). Therefore, it is conceivable that a similar process occursin the plant itself, or more likely, in dry leaf material that has been exposed to air forconsiderable periods of time, with strongly colored phytochemicals (e.g. porphyrins) serving as aScheme S1. Preparation of Semi-Synthetic AnalogsNHNHOMeMeO2COMeEtSH, AlCl3CH2Cl20 C to R.T.0.5 hNHNHOHMeO2COMe91%B/NNHMeOMeO2COMeOHNHNHOMeMeO2COMeMeCN/H2O0 °C1) O2, lightrose bengalMeOH, 0°C2) Na2SO3H2O/MeOHR.T.PIFAorA/PIFA = 29%orO2 = 58% (NMR yield)air = 34%1 = 9-hydroxycorynantheidineS10substitute for rose bengal. This phenomenon may account for the observation of 7-OH in somesamples of Mitragyna speciosa, but not in those analyzed in the present report.
Source
Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators J. Am. Chem. Soc. 2016, 138, 21, 6754–6764 Publication Date:May 18, 2016 https://doi.org/10.1021/jacs.6b00360
Sources
Malaysian JHournal of Analytical Sciences
A SIMPLE AND COST EFFECTIVE ISOLATION AND PURIFICATION PROTOCOL OF MITRAGYNINE FROM MITRAGYNA SPECIOSA KORTH (KETUM) LEAVES (Satu Protokol Pengasingan Mitragina daripada Daun Mitragyna speciosa Korth (Ketum) yang Mudah dan Kos Efektif Goh Teik Beng1* , Mohamad Razak Hamdan1, Mohammad Jamshed Siddiqui2, Mohd Nizam Mordi1 and Sharif Mahsufi Mansor1 1Centre of Drug Research, 2 School of Pharmaceutical Science, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia. *Corresponding author: gtb.dd04@student.usm.my
ACS
7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects Andrew C. Kruegel, Rajendra Uprety, Steven G. Grinnell, Cory Langreck, Elizabeth A. Pekarskaya, Valerie Le Rouzic, Michael Ansonoff, Madalee M. Gassaway, John E. Pintar, Gavril W. Pasternak, Jonathan A. Javitch, Susruta Majumdar, and Dalibor Sames ACS Central Science 2019 5 (6), 992-1001 DOI: 10.1021/acscentsci.9b00141
(see supporting documentation for methods)^^^
other useful information
https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.1c01273
Lab Notes
Required Solvents (extraction isolation)
Chloroform - make from acetone and bleach
Petroleum ether (not actually an ether by any chemical means)- (consists of mostly hexanes and Pentanes), byuproduct of fuel production, carries an entourage of aliphatic hydrocarbons- Buying online somewhere...Serves as a defatting agent -
Not necessary but for clarification purposes*** Diethyl ether - derivable from starter fluid when separated into diethyl ether and hexane. A single petroleum will be used, hexane, due to its availability. Hexane will be separated from john deere starter fluid (~20% hexane)
Required solvents/reagents for conversion
Oxone - relatively cheap
NaHCO3 - derp
Acetone - easily buy
EtOAc- ethyl acetate - can make from combination of alcohol and glacial acetic acid (GAA made from vinegar OR sulfuric acid with sodium acetate) with strong acid catalyst
tri ethyl amine - easily purchasable
Extraction and isolation of mitragynine
Below is presented the scheme from Mohamad Razak et al.
This is the original scheme and will be corrected for the use of 2L of solvent everything down by half
Fresh Mitragyna speciosa Korth leaves (1.0 kg) were washed with water to remove dirt and adhering material, oven dried at 45-50 °C for three days and milled into fine powder using a blender to get the dry powder (297.0 g). Soxhlet extraction was carried out using 297.0 g powdered leaves with 4 L petroleum ether (40-60 oC) for 8 hour, then petroleum ether solution was discarded and the defatted powdered leaves were dried and the extraction was repeated with 4 L chloroform for 8 hour. The chloroform solution obtained was filtered, concentrated, evaporated to dryness under the reduced pressure using rotary evaporator and was kept in a refrigerator (-200C). The dried crude chloroform extract was subjected for flash chromatography according to the method of Still et al.[10]. Crude fraction containing mitragynine was obtained by eluting with hexane and ethyl acetate (80:20 v/v) and this fraction (100 mL) was subjected to liquid-liquid fractionation using petroleum ether (100 mL X 3 times) for further purification. The petroleum ether layer was discarded and the remaining solution was concentrated under the reduced pressure using a Buchi R215 Rotavapor (Flawil, Switzerland) to obtain crude mitragynine.
Corrected scheme
148.5 g of starting material is soxhlet extracted for 8 hours, first in 2L of petroleum ether, then in 2L of chloroform. Ether solution is discarded and the chloroform fraction is rotovapped to dryness, the chloroform is reclaimed and crude extract isolated. Dried crude chloroform extract was subjected to flash chromatography according to Still et al. (general procedure below).
Chromatography fraction was obtained from the Crude fraction using 80:20 V/V and this 100mL fraction was subjected to liquid liquid extraction using 100mL petroleum ether 3 times for further purification via a separatory funnel. Discard pet. ether and concentrate remaining solution under roto-vap to obtain crude mitragynine.
Purification by recrystallization will not be sought in this exp.
Mitragynine to 7-OH Conversion Method
7-Hydroxymitragynine: Oxone Oxidation
To a solution of mitragynine (199 mg, 0.500 mmol) in acetone (15 mL), was added saturated aqueous NaHCO 3 (10 mL), and the mixture was cooled to 0 °C. A solution of Oxone monopersulfate (2KHSO 5 · KHSO 4 · K2 SO4 , MW = 615.5; 308 mg, 0.500 mmol) in water (5 mL) was then added dropwise over 25 minutes and the mixture left to stir at 0 °C for an additional 15 minutes. At this time, the reaction was diluted with water (60 mL) and extracted with EtOAc (3 x 30 mL). The combined organics were washed with brine (30 mL), dried over Na2 SO4 , and concentrated in vacuo to give the crude product as a pale-orange foam (170 mg). This material was purified by column chromatography (6:4 hexanes:EtOAc + 2% Et3 N) to provide pure 7-hydroxymitragynine as an amorphous, pale-yellow solid (115 mg, 55%). Spectral and physical properties were in agreement with those previously reported.1
It is worth nothing, room temp exposure to oxygen and UV light also performs this reaction, albeit to a much lower yield, ~8%.
Source:
Supporting information containing exact methods
Flash Chromatography. General Procedure via Stil et al.
Flash Chromatography. General Procedure. First a low viscosity solvent system (e.g., ethyl acetateh0-60 "C petroleum etherla is found which separates the mixture and moves the desired component on analytical TLC to an Rf of 0.35.9If several compounds are to be separated which run very close on TLC, adjust the solvent to put the midpoint between the components at Rf = 0.35. If the compounds are widely separated, adjust the R, of the less mobile component to
0.35. Having chosen the solvent, a column of the appropriate diameter (see text, Table I) is selected and a small plug of glass wool is placed in the tube connecting the stopcock to the column body (A in the diagram above). Two telescoping lengths of glass tubing (6and 8 mm
0.d.) make placement of the glass wool plug easy. Next a smooth '/a in. layer of 50-100 mesh sand is added to cover the bottom of the column and dry 40-63 pm silica gel is poured into the column in a single portion to give a depth of 5.5-6 in. With the stopcock open, the column is gently tapped vertically on the bench top to pack the gel. Next a l/a in. layer of sand is carefully placed on the flat top of the dry gel bed and the column is clamped for pressure packing and elution. The solvent chosen above is then poured carefully over the sand to fill the column completely. The needle valve (B) of the flow controller is opened all the way and the flow controller is fitted tightly to the top of the column and secured with strong rubber bands. The main air line valve leading to the flow controller is opened slightly and a finger is placed fairly tightly over the bleed port (C). This will cause the pressure above the adsorbent bed to climb rapidly and compress the silica gel as solvent is rapidly forced through the column. It is important to maintain the pressure until all the air is expelled and the lower part of the column is cool; otherwise, the column will fragment and should be repacked unless the separation desired is a trivial one. Particular care is necessary with large diameter columns. The pressure is then released and excess eluant is forced out of the column above the adsorbent bed by partially blocking the bleed port (C). The top of the silica gel should not be allowed to run dry. Next the sample is applied by pipette as a 20-250% solution in the eluant to the top of the adsorbent bed and the flow controller is briefly placed on top of the column to push all of the sample into the silica gel." The solvent used to pack the column is ordinarily reused to elute the column. The walls of the column are washed down with a few milliliters of fresh eluant, the washings are pushed into the gel as before, and the column is carefully filled with eluant so as not to disturb the adsorbent bed. The flow controller is finally secured to the column and adjusted to cause the surface of the solvent in the column to fall 2.0 in./min. This seems to be an optimum value of the flow rate for most low viscosity solvents for any column diameter with the 40-63 km silica gel. Fractions are
collected until all the solvent has been used (see Table I to estimate the amount of solvent and fraction size). It is best not to let the column run dry since further elution is occasionally necessary. Purified components are identified as described in the text by TLC. If the foregoing instructions are followed exactly, there is little opportunity for the separation to fail.
Although we generally pack fresh columns for each separation,the expense of large-scale separations makes it advantageous to reuse large diameter columns. Column recycling is effected by first flushing (rate = 2 in./min) the column with approximately 5 in. of the more polar component in the eluant (generally ethyl acetate or acetone) and then with 5 in. of the desired eluant. If the eluant is relatively nonpolar (e.g., 110% EtOAc/petroleum ether), it may be more advisable to use a flushing solvent (e.g., 2040% EtOAc/petroleum ether) which is somewhat less polar than the pure high polarity component.
Older less effective isolation technique described here, just for comparative purposes
Isolation of Mitragyna speciosa Alkaloids. Dry, finely powdered Mitragyna speciosaleaves (186 g) (Thai strain, Arena Ethnobotanicals, Del Mar, CA) were extracted repeatedly withboiling MeOH (4 x 500 mL), vacuum filtering the solids thoroughly between each extraction.The combined extracts were concentrated to provide a dark green-black solid (56.19 g). Thismaterial was crushed and extracted twice with room temperature 10% aqueous AcOH (2 x 300mL), filtering each extract through celite (slow). The combined, coffee-colored acidic extracts,were washed with hexanes (2 x 150 mL) and carefully basified (with ice cooling) to pH 8-9using concentrated aqueous NaOH (thick tan precipitate forms). The basic mixture was thenextracted thoroughly with CHCl3 (6 x 200 mL, emulsions), shaking vigorously with eachextraction (not all solids dissolve). The combined organics were washed with water (2 x 400mL), dried over Na2SO4, and concentrated to yield the crude alkaloid fraction as a foamy brownsolid (3.62 g, 1.9 mass%). TLC analysis of this material revealed four distinct spots(mitragynine, paynantheine, speciogynine, and speciociliatine in order of increasing polarity), inaddition to baseline. The crude alkaloid mixture was separated by column chromatography (8:2→ 7:3 → 6:4 → 1:1 hexanes:EtOAc + 2% Et3N, 2 column volumes each) to provide fractionscontaining pure mitragynine (1.38 g), mitragynine + minor paynantheine and speciogynine (0.25g), paynantheine and speciogynine + minor mitragynine and speciociliatine (0.61 g),speciociliatine + minor paynantheine and speciogynine (0.20 g), and speciociliatine + minorimpurities (0.20 g). These mixed fractions were further separated by repeated columnchromatography (gradients of hexanes:EtOAc mixtures, with or without 2% Et3N) to provideadditional mitragynine (190 mg), along with pure samples of paynantheine (46 mg),speciogynine (12 mg), and speciociliatine (148 mg). The total yield of isolated mitragynine was1.57 g (0.84 mass%), and of total mixed paynantheine, speciogynine, and speciocoliatine was S191.01 g (0.54 mass%). However, the yields for the pure samples of the minor alkaloids should notbe considered indicative of the quantities contained in the plant material, due to purificationlosses.This isolation procedure was repeated a second time on a larger, separate batch ofpowdered Mitragyna speciosa leaves (454 g), scaling quantities appropriately. It should be notedthat in this second extraction, it was found that basification of the aqueous extracts to pH 12(instead of 8-9) was beneficial, as it prevented the formation of emulsions in the subsequentCHCl3 extractions. This extraction provided the crude alkaloid fraction as a foamy, greenishbrown solid (8.03 g, 1.8 mass%). The mixed alkaloids were separated by columnchromatography as before, to provide pure mitragynine (3.33 g, 0.73 mass%) and fractionscontaining mixtures of the minor alkaloids (total >3 g). No effort was made to further purifypaynantheine, speciogynine, and speciociliatine from the mixed fractions, but the ratios betweenthese alkaloids clearly differed from the first extraction, with speciociliatine being significantlymore prevalent. Mitragynine. Isolated as an amorphous, pale-yellow solid.
Previous Oxidation/conversion techniques reported...
Mitragynine was easily oxidized to 7-hydroxymitragynine (7-OH) by the literature procedure1 employing the hypervalent iodinespecies [bis(trifluoroacetoxy)iodo]benzene (PIFA), but this reaction produced numerousbyproducts and was low yielding. It was also found that the same transformation could beperformed cleanly using singlet oxygen generated by irradiation with visible light in the presenceof rose bengal, under air or pure O2 atmosphere, but yields were still modest (Scheme S1A).Interestingly, it was also found that this photooxidation reaction could take place at roomtemperature under sunlight illumination, with no need for the addition of an external reducingagent, albeit in low yield (8% by NMR). Therefore, it is conceivable that a similar process occursin the plant itself, or more likely, in dry leaf material that has been exposed to air forconsiderable periods of time, with strongly colored phytochemicals (e.g. porphyrins) serving as aScheme S1. Preparation of Semi-Synthetic AnalogsNHNHOMeMeO2COMeEtSH, AlCl3CH2Cl20 C to R.T.0.5 hNHNHOHMeO2COMe91%B/NNHMeOMeO2COMeOHNHNHOMeMeO2COMeMeCN/H2O0 °C1) O2, lightrose bengalMeOH, 0°C2) Na2SO3H2O/MeOHR.T.PIFAorA/PIFA = 29%orO2 = 58% (NMR yield)air = 34%1 = 9-hydroxycorynantheidineS10substitute for rose bengal. This phenomenon may account for the observation of 7-OH in somesamples of Mitragyna speciosa, but not in those analyzed in the present report.
Source
Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators J. Am. Chem. Soc. 2016, 138, 21, 6754–6764 Publication Date:May 18, 2016 https://doi.org/10.1021/jacs.6b00360
Sources
Malaysian JHournal of Analytical Sciences
A SIMPLE AND COST EFFECTIVE ISOLATION AND PURIFICATION PROTOCOL OF MITRAGYNINE FROM MITRAGYNA SPECIOSA KORTH (KETUM) LEAVES (Satu Protokol Pengasingan Mitragina daripada Daun Mitragyna speciosa Korth (Ketum) yang Mudah dan Kos Efektif Goh Teik Beng1* , Mohamad Razak Hamdan1, Mohammad Jamshed Siddiqui2, Mohd Nizam Mordi1 and Sharif Mahsufi Mansor1 1Centre of Drug Research, 2 School of Pharmaceutical Science, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia. *Corresponding author: gtb.dd04@student.usm.my
ACS
7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects Andrew C. Kruegel, Rajendra Uprety, Steven G. Grinnell, Cory Langreck, Elizabeth A. Pekarskaya, Valerie Le Rouzic, Michael Ansonoff, Madalee M. Gassaway, John E. Pintar, Gavril W. Pasternak, Jonathan A. Javitch, Susruta Majumdar, and Dalibor Sames ACS Central Science 2019 5 (6), 992-1001 DOI: 10.1021/acscentsci.9b00141
(see supporting documentation for methods)^^^
other useful information
https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.1c01273
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