CN108314641A - A kind of preparation method of natural products Norpsilocin - Google Patents
A kind of preparation method of natural products Norpsilocin Download PDFInfo
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- CN108314641A CN108314641A CN201711448672.9A CN201711448672A CN108314641A CN 108314641 A CN108314641 A CN 108314641A CN 201711448672 A CN201711448672 A CN 201711448672A CN 108314641 A CN108314641 A CN 108314641A
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- norpsilocin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Abstract
The invention discloses a kind of preparation method of the preparation method of natural products Norpsilocin, this method is realized by following steps：1) tryptamines is dissolved in organic mixed solution and is cooled to 10~0 DEG C, organic mixed solution of the dropwise addition containing iodine under stirring, being again heated to room temperature after being added dropwise to complete is reacted, and later, is quenched, extracted, is dried and concentrated, and intermediate product is obtained；2) above-mentioned intermediate product is dissolved in organic solvent and is heated, it is added with stirring Ethyl formate, after completion of the reaction, system is cooled to 10~0 DEG C again and reducing agent is added the reaction was continued, later, it is quenched, extracted, being dried, concentrating simultaneously column chromatography for separation, obtaining natural products Norpsilocin.The present invention uses the tryptamines being commercially easy to get, Ethyl formate as starting material, and synthesize Norpsilocin under the catalysis of bismuth acetate, stannous chloride and reducing agent (lithium aluminium hydride reduction), preparation method is simple, and for operating procedure compared to being reduced, synthesis cost is low；Convenient separation, yield is high, and selectivity is good.
Description
Technical field
The invention belongs to natural products synthesis technical fields, are related to a kind of preparation method of natural products Norpsilocin.
Background technology
Norpsilocin is a kind of novel indoles alkaloid natural products, is German Dirk Hoffmeister classes
Topic group is to having found in the research for causing unreal toxicity light lid umbrella mushroom Psilocybe cubensis； (Claudius
Lenz, Jonas Wick, Dirk Hoffmeister, J.Nat.Prod.2017,80,2835-2838).The natural products is being tied
On structure with natural products Baeocystin (Leung AY, Paul AG Journal of Pharmaceutical
Sciences.1968,57,1667-1671.) there is identical basic molecular structure, but this compound there is no at present
Preparation method；This case provides a kind of preparation method of brief and practical for Norpsilocin.
Invention content
In view of this, the purpose of the present invention is to provide a kind of preparation methods of natural products Norpsilocin.
In order to achieve the above objectives, the technical proposal of the invention is realized in this way：A kind of natural products Norpsilocin
Preparation method, this method realized by following steps：
Step 1, tryptamines is dissolved in organic mixed solution and is cooled to -10~0 DEG C, dropwise addition is organic mixed containing iodine under stirring
Solution is closed, room temperature is again heated to after being added dropwise to complete and is reacted, later, be quenched, extracted, be dried and concentrated, is obtained intermediate
Product；
Step 2, the intermediate product that the step 1 obtains is dissolved in organic solvent and is heated to 90~100 DEG C, under stirring
Ethyl formate is added, waits for after completion of the reaction, then system is cooled to -10~0 DEG C and reducing agent is added the reaction was continued, later, into
Row is quenched, extracts, drying, concentrating and column chromatography for separation, obtains natural products Norpsilocin.
Preferably, in the step 1, organic mixed solution is the mixed liquor of acetic acid, sodium acetate and water.
Preferably, in the step 1, the molar ratio of the tryptamines and sodium acetate in organic mixed solution is 1：(1~2).
Preferably, in the step 1, the specific preparation method of organic mixed solution containing iodine is：Iodine is dissolved in four
In hydrogen furans, it is added with stirring bismuth acetate, stannous chloride, acetic acid and water, obtains organic mixed solution containing iodine.
Preferably, in the step 1, iodine in the tryptamines and organic mixed solution containing iodine, bismuth acetate, stannous chloride
Molar ratio is 1：(1~1.5)：(0.1~0.5)：(0.3~0.8).
Preferably, in the step 1, the reaction time is 8~12h.
Preferably, in the step 2, the molar ratio of the intermediate product and Ethyl formate is 1：(3~5).
Preferably, in the step 2, the organic solvent is tetrahydrofuran (THF), dichloromethane (CH2Cl2), ether
At least one of, preferably tetrahydrofuran (THF).
Preferably, in the step 2, it is described be added Ethyl formate when reaction time be 10~20h；The addition reduction
Reaction time when agent is 1~3h.
Preferably, in the step 2, the reducing agent is lithium aluminium hydride reduction (LiAlH4), sodium borohydride (NaBH4) in extremely
Few one kind, preferably lithium aluminium hydride reduction (LiAlH4).
Compared with the existing technology, the present invention uses the tryptamines being commercially easy to get, Ethyl formate as starting material, and in acetic acid
Norpsilocin is synthesized under the catalysis of bismuth, stannous chloride and reducing agent (lithium aluminium hydride reduction), preparation method is simple, operating procedure
Compared to being reduced, synthesis cost is low；Convenient separation, yield is high, and selectivity is good, and the reagent used is common agents, honest and clean
Valence is easy to get.
Specific implementation mode
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to the accompanying drawings and embodiments, right
The present invention is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, and
It is not used in the restriction present invention.
The present invention provides a kind of preparation method of natural products Norpsilocin, reaction equation is as follows：
This method is realized by following steps：
Step 1, tryptamines is dissolved in organic mixed solution and is cooled to -10~0 DEG C, dropwise addition (I containing iodine under stirring2)
Organic mixed solution is again heated to room temperature and carries out 8~12h of reaction after being added dropwise to complete, later, be quenched, extracted, dried and is dense
Contracting obtains intermediate product；
Wherein, organic mixed solution is the mixed liquor of acetic acid, sodium acetate and water；Tryptamines and sodium acetate in organic mixed solution
Molar ratio be 1：(1~2)；Containing iodine (I2) the specific preparation method of organic mixed solution be：By iodine (I2) it is dissolved in tetrahydrofuran
(THF) in, it is added with stirring bismuth acetate, stannous chloride, acetic acid and water, obtains organic mixed solution containing iodine；Tryptamines with contain iodine
Organic mixed solution in iodine (I2), bismuth acetate, stannous chloride molar ratio be 1：(1~1.5)：(0.1~0.5)：(0.3~
0.8)；Iodine (I is added dropwise2) speed be 5~20 drops/min；
Step 2, the intermediate product that the step 1 obtains is dissolved in organic solvent and is heated to 90~100 DEG C, under stirring
Ethyl formate is added and reacts 10~20h, waits for after completion of the reaction, then system is cooled to -10~0 DEG C and reducing agent is added and is continued instead
1~3h is answered, later, is quenched, extracted, dried, concentrating simultaneously column chromatography for separation, obtaining natural products Norpsilocin；
Wherein, the molar ratio of intermediate product and Ethyl formate is 1：(3~5)；Organic solvent is tetrahydrofuran, dichloromethane
At least one of alkane, ether, preferably tetrahydrofuran (THF)；Reducing agent is lithium aluminium hydride reduction (LiAlH4), sodium borohydride
(NaBH4At least one of), preferably lithium aluminium hydride reduction (LiAlH4)。
Compared with the existing technology, the present invention uses the tryptamines being commercially easy to get, Ethyl formate as starting material, and in acetic acid
Norpsilocin is synthesized under the catalysis of bismuth, stannous chloride and reducing agent (lithium aluminium hydride reduction), preparation method is simple, operating procedure
Compared to being reduced, synthesis cost is low；Convenient separation, yield is high, and selectivity is good, and the reagent used is common agents, honest and clean
Valence is easy to get.
Embodiment 1
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 1.5mol:5) it is molten that organic mixing containing tryptamines is made in mixed liquor
Liquid is simultaneously cooled to 0 DEG C；Under the protection of nitrogen, by the iodine (I of 1mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added four
Hydrogen furans (THF) stirs evenly, and adds the bismuth acetate of 0.3mol, the stannous chloride of 0.5mol, acetic acid and water (acetic acid and water
Volume ratio be 1:5) it is made containing iodine (I2) organic mixed solution；At 0 DEG C, by the above-mentioned (I containing iodine2) organic mixed solution
It is slowly dropped into the organic solution containing tryptamines of 0 DEG C of (speed of instillation be 5~20 drops/min), room is heated to after being added dropwise to complete
Temperature carries out reaction 10h, later, with saturation K2CO3Aqueous solution is quenched, and ethyl acetate extraction collects organic phase and uses anhydrous sodium sulfate
Dry, concentration, obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 4mol is added reacts 15h, waits for after completion of the reaction, then system is cooled to 0 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 1h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 91.1%) is obtained.
Embodiment 2
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 1.5mol:5) it is molten that organic mixing containing tryptamines is made in mixed liquor
Liquid is simultaneously cooled to -10 DEG C；Under the protection of nitrogen, by the iodine (I of 1mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added
Tetrahydrofuran (THF) stirs evenly, add the bismuth acetate of 0.3mol, the stannous chloride of 0.5mol, acetic acid and water (acetic acid and
The volume ratio of water is 1:5) it is made containing iodine (I2) organic mixed solution；At -10 DEG C, by the above-mentioned (I containing iodine2) organic mixing
Solution is slowly dropped into the organic solution containing tryptamines of -10 DEG C of (speed of instillation be 5~20 drops/min), is heated after being added dropwise to complete
Reaction 12h is carried out to room temperature, later, with saturation K2CO3Aqueous solution is quenched, and ethyl acetate extraction collects organic phase and with anhydrous sulphur
Sour sodium is dry, concentrates, and obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 4mol is added reacts 10h, waits for after completion of the reaction, then system is cooled to -10 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 2h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 90.6%) is obtained.
Embodiment 3
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 1.5mol:5) it is molten that organic mixing containing tryptamines is made in mixed liquor
Liquid is simultaneously cooled to 0 DEG C；Under the protection of nitrogen, by the iodine (I of 1mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added four
Hydrogen furans (THF) stirs evenly, and adds the bismuth acetate of 0.3mol, the stannous chloride of 0.5mol, acetic acid and water (acetic acid and water
Volume ratio be 1:5) it is made containing iodine (I2) organic mixed solution；At 0 DEG C, by the above-mentioned (I containing iodine2) organic mixed solution
It is slowly dropped into the organic solution containing tryptamines of 0 DEG C of (speed of instillation be 5~20 drops/min), room is heated to after being added dropwise to complete
Temperature carries out reaction 8h, later, with saturation K2CO3Aqueous solution is quenched, and ethyl acetate extraction collects organic phase and uses anhydrous sodium sulfate
Dry, concentration, obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 4mol is added reacts 20h, waits for after completion of the reaction, then system is cooled to 0 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 3h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 89.3%) is obtained.
Embodiment 4
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 1.5mol:5) it is molten that organic mixing containing tryptamines is made in mixed liquor
Liquid is simultaneously cooled to 0 DEG C；Under the protection of nitrogen, by the iodine (I of 1mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added four
Hydrogen furans (THF) stirs evenly, and adds the bismuth acetate of 0.3mol, the stannous chloride of 0.5mol, acetic acid and water (acetic acid and water
Volume ratio be 1:5) it is made containing iodine (I2) organic mixed solution；At 0 DEG C, by the above-mentioned (I containing iodine2) organic mixed solution
It is slowly dropped into the organic solution containing tryptamines of 0 DEG C of (speed of instillation be 5~20 drops/min), room is heated to after being added dropwise to complete
Temperature carries out reaction 12h, later, with saturation K2CO3Aqueous solution is quenched, and ethyl acetate extraction collects organic phase and uses anhydrous sodium sulfate
Dry, concentration, obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 4mol is added reacts 10h, waits for after completion of the reaction, then system is cooled to 0 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 2h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 90.7%) is obtained.
Embodiment 5
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 1mol:5) organic mixed solution containing tryptamines is made in mixed liquor
And it is cooled to 0 DEG C；Under the protection of nitrogen, by the iodine (I of 1.2mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added four
Hydrogen furans (THF) stirs evenly, and adds the bismuth acetate of 0.1mol, the stannous chloride of 0.3mol, acetic acid and water (acetic acid and water
Volume ratio be 1:5) it is made containing iodine (I2) organic mixed solution；At 0 DEG C, by the above-mentioned (I containing iodine2) organic mixed solution
It is slowly dropped into the organic solution containing tryptamines of 0 DEG C of (speed of instillation be 5~20 drops/min), room temperature is heated to after being added dropwise to complete
Reaction 10h is carried out, later, with saturation K2CO3Aqueous solution is quenched, ethyl acetate extraction, collects organic phase and is done with anhydrous sodium sulfate
Dry, concentration, obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 3mol is added reacts 15h, waits for after completion of the reaction, then system is cooled to 0 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 1h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 90.2%) is obtained.
Embodiment 6
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 1mol:5) organic mixed solution containing tryptamines is made in mixed liquor
And it is cooled to -10 DEG C；Under the protection of nitrogen, by the iodine (I of 1.2mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added
Tetrahydrofuran (THF) stirs evenly, add the bismuth acetate of 0.1mol, the stannous chloride of 0.3mol, acetic acid and water (acetic acid and
The volume ratio of water is 1:5) it is made containing iodine (I2) organic mixed solution；At -10 DEG C, by the above-mentioned (I containing iodine2) organic mixing
Solution is slowly dropped into the organic solution containing tryptamines of -10 DEG C of (speed of instillation be 5~20 drops/min), is heated after being added dropwise to complete
Reaction 12h is carried out to room temperature, later, with saturation K2CO3Aqueous solution is quenched, and ethyl acetate extraction collects organic phase and with anhydrous sulphur
Sour sodium is dry, concentrates, and obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 3mol is added reacts 10h, waits for after completion of the reaction, then system is cooled to -10 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 2h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 88.4%) is obtained.
Embodiment 7
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 1mol:5) organic mixed solution containing tryptamines is made in mixed liquor
And it is cooled to 0 DEG C；Under the protection of nitrogen, by the iodine (I of 1.2mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added four
Hydrogen furans (THF) stirs evenly, and adds the bismuth acetate of 0.1mol, the stannous chloride of 0.3mol, acetic acid and water (acetic acid and water
Volume ratio be 1:5) it is made containing iodine (I2) organic mixed solution；At 0 DEG C, by the above-mentioned (I containing iodine2) organic mixed solution
It is slowly dropped into the organic solution containing tryptamines of 0 DEG C of (speed of instillation be 5~20 drops/min), room is heated to after being added dropwise to complete
Temperature carries out reaction 8h, later, with saturation K2CO3Aqueous solution is quenched, and ethyl acetate extraction collects organic phase and uses anhydrous sodium sulfate
Dry, concentration, obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 3mol is added reacts 20h, waits for after completion of the reaction, then system is cooled to 0 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 3h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 86.5%) is obtained.
Embodiment 8
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 1mol:5) organic mixed solution containing tryptamines is made in mixed liquor
And it is cooled to 0 DEG C；Under the protection of nitrogen, by the iodine (I of 1.2mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added four
Hydrogen furans (THF) stirs evenly, and adds the bismuth acetate of 0.1mol, the stannous chloride of 0.3mol, acetic acid and water (acetic acid and water
Volume ratio be 1:5) it is made containing iodine (I2) organic mixed solution；At 0 DEG C, by the above-mentioned (I containing iodine2) organic mixed solution
It is slowly dropped into the organic solution containing tryptamines of 0 DEG C of (speed of instillation be 5~20 drops/min), room is heated to after being added dropwise to complete
Temperature carries out reaction 12h, later, with saturation K2CO3Aqueous solution is quenched, and ethyl acetate extraction collects organic phase and uses anhydrous sodium sulfate
Dry, concentration, obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 3mol is added reacts 10h, waits for after completion of the reaction, then system is cooled to 0 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 2h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 87.2%) is obtained.
Embodiment 9
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 2mol:5) organic mixed solution containing tryptamines is made in mixed liquor
And it is cooled to 0 DEG C；Under the protection of nitrogen, by the iodine (I of 1.5mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added four
Hydrogen furans (THF) stirs evenly, and adds the bismuth acetate of 0.5mol, the stannous chloride of 0.8mol, acetic acid and water (acetic acid and water
Volume ratio be 1:5) it is made containing iodine (I2) organic mixed solution；At 0 DEG C, by the above-mentioned (I containing iodine2) organic mixed solution
It is slowly dropped into the organic solution containing tryptamines of 0 DEG C of (speed of instillation be 5~20 drops/min), room is heated to after being added dropwise to complete
Temperature carries out reaction 10h, later, with saturation K2CO3Aqueous solution is quenched, and ethyl acetate extraction collects organic phase and uses anhydrous sodium sulfate
Dry, concentration, obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 5mol is added reacts 15h, waits for after completion of the reaction, then system is cooled to 0 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 1h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 89.7%) is obtained.
Embodiment 10
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 2mol:5) organic mixed solution containing tryptamines is made in mixed liquor
And it is cooled to -10 DEG C；Under the protection of nitrogen, by the iodine (I of 1.5mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added
Tetrahydrofuran (THF) stirs evenly, add the bismuth acetate of 0.5mol, the stannous chloride of 0.8mol, acetic acid and water (acetic acid and
The volume ratio of water is 1:5) it is made containing iodine (I2) organic mixed solution；At -10 DEG C, by the above-mentioned (I containing iodine2) organic mixing
Solution is slowly dropped into the organic solution containing tryptamines of -10 DEG C of (speed of instillation be 5~20 drops/min), is heated after being added dropwise to complete
Reaction 12h is carried out to room temperature, later, with saturation K2CO3Aqueous solution is quenched, and ethyl acetate extraction collects organic phase and with anhydrous sulphur
Sour sodium is dry, concentrates, and obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 5mol is added reacts 10h, waits for after completion of the reaction, then system is cooled to -10 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 2h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 87.4%) is obtained.
Embodiment 11
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 2mol:5) organic mixed solution containing tryptamines is made in mixed liquor
And it is cooled to 0 DEG C；Under the protection of nitrogen, by the iodine (I of 1.5mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added four
Hydrogen furans (THF) stirs evenly, and adds the bismuth acetate of 0.5mol, the stannous chloride of 0.8mol, acetic acid and water (acetic acid and water
Volume ratio be 1:5) it is made containing iodine (I2) organic mixed solution；At 0 DEG C, by the above-mentioned (I containing iodine2) organic mixed solution
It is slowly dropped into the organic solution containing tryptamines of 0 DEG C of (speed of instillation be 5~20 drops/min), room is heated to after being added dropwise to complete
Temperature carries out reaction 8h, later, with saturation K2CO3Aqueous solution is quenched, and ethyl acetate extraction collects organic phase and uses anhydrous sodium sulfate
Dry, concentration, obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 5mol is added reacts 20h, waits for after completion of the reaction, then system is cooled to 0 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 3h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 90.5%) is obtained.
Embodiment 12
Step 1, under the protection of nitrogen, the tryptamines of 1mol is placed in the processed eggplant bottle of anhydrous and oxygen-free, is added
(volume ratio of acetic acid and water is 1 to sodium acetate, acetic acid and the water of 2mol:5) organic mixed solution containing tryptamines is made in mixed liquor
And it is cooled to 0 DEG C；Under the protection of nitrogen, by the iodine (I of 1.5mol2) be placed in the processed eggplant bottle of anhydrous and oxygen-free and be added four
Hydrogen furans (THF) stirs evenly, and adds the bismuth acetate of 0.5mol, the stannous chloride of 0.8mol, acetic acid and water (acetic acid and water
Volume ratio be 1:5) it is made containing iodine (I2) organic mixed solution；At 0 DEG C, by the above-mentioned (I containing iodine2) organic mixed solution
It is slowly dropped into the organic solution containing tryptamines of 0 DEG C of (speed of instillation be 5~20 drops/min), room is heated to after being added dropwise to complete
Temperature carries out reaction 12h, later, with saturation K2CO3Aqueous solution is quenched, and ethyl acetate extraction collects organic phase and uses anhydrous sodium sulfate
Dry, concentration, obtains intermediate product；
Step 2, the intermediate product that 1mol steps 1 obtain is dissolved in tetrahydrofuran (THF) and is heated to 100 DEG C, stirring
The lower Ethyl formate that 5mol is added reacts 10h, waits for after completion of the reaction, then system is cooled to 0 DEG C and lithium aluminium hydride reduction is added
(LiAlH4) the reaction was continued 2h is quenched, ethyl acetate extraction later with ice water, collect organic phase and it is dry with anhydrous sodium sulfate,
Simultaneously column chromatography for separation is concentrated, natural products Norpsilocin (yield 89.5%) is obtained.
It spectrogram testing result and is analyzed as follows：
Magnetic resonance detection is carried out to 1 products therefrom of embodiment, the hydrogen spectrogram of 1 products therefrom of embodiment obtains specific detection
Data are：1H NMR(CD3OD, 400MHz)：δ=7.01 (s, 1H), 6.38 (dd, J=7.4,1.0Hz, 1H), 6.91 (dd, J
=8,7.4Hz, 1H), 6.88, (dd, J=8.1,1.0Hz, 1H), 3.40 (t, J=6.8Hz, 2H), 3.25 (t, J=6.9Hz,
2H), 2.70 (s, 3H)13C NMR(CD3OD, 400MHz)：153.0,141.3,124.3,123.4,118.2,110.7,
105.0,104.4,52.8,34.0,25.4. can be seen that the natural products that this method is prepared by detection data
H atom in Norpsilocin in different chemical environments goes out peak position stabilization, and free from admixture peak, purity is high, and separation property is good, yield
It is high.
Due to embodiment 2 to the testing number of the detection data and 1 products therefrom of embodiment of 12 any products therefrom of embodiment
According to identical, therefore, data analysis no longer is carried out to 12 any products therefrom of embodiment to implementing 2.
The foregoing is only a preferred embodiment of the present invention, is not intended to limit the scope of the present invention.
Claims (10)
1. a kind of preparation method of natural products Norpsilocin, which is characterized in that this method is realized by following steps：
Step 1, tryptamines is dissolved in organic mixed solution and is cooled to -10~0 DEG C, it is molten that organic mixing containing iodine is added dropwise under stirring
Liquid is again heated to room temperature after being added dropwise to complete and is reacted, and later, is quenched, extracted, is dried and concentrated, and intermediate product is obtained；
Step 2, the intermediate product that the step 1 obtains is dissolved in organic solvent and is heated to 90~100 DEG C, be added with stirring
Ethyl formate waits for after completion of the reaction, then system is cooled to -10~0 DEG C and reducing agent is added the reaction was continued, later, quenches
It goes out, extract, drying, concentrating simultaneously column chromatography for separation, obtaining natural products Norpsilocin.
2. the preparation method of natural products Norpsilocin according to claim 1 a kind of, which is characterized in that the step
In rapid 1, organic mixed solution is the mixed liquor of acetic acid, sodium acetate and water.
3. the preparation method of natural products Norpsilocin according to claim 2 a kind of, which is characterized in that the step
In rapid 1, the molar ratio of the tryptamines and sodium acetate in organic mixed solution is 1：(1~2).
4. the preparation method of natural products Norpsilocin according to claim 3 a kind of, which is characterized in that the step
In rapid 1, the specific preparation method of organic mixed solution containing iodine is：Iodine is dissolved in tetrahydrofuran, second is added with stirring
Sour bismuth, stannous chloride, acetic acid and water obtain organic mixed solution containing iodine.
5. the preparation method of natural products Norpsilocin according to claim 4 a kind of, which is characterized in that the step
In rapid 1, iodine in the tryptamines and organic mixed solution containing iodine, bismuth acetate, stannous chloride molar ratio be 1：(1~1.5)：
(0.1~0.5)：(0.3~0.8).
6. the preparation method of natural products Norpsilocin according to claim 5 a kind of, which is characterized in that the step
In rapid 1, the reaction time is 8~12h.
7. the preparation method of natural products Norpsilocin according to claim 6 a kind of, which is characterized in that the step
In rapid 2, the molar ratio of the intermediate product and Ethyl formate is 1：(3~5).
8. the preparation method of natural products Norpsilocin according to claim 7 a kind of, which is characterized in that the step
In rapid 2, the organic solvent is at least one of tetrahydrofuran, dichloromethane, ether.
9. the preparation method of natural products Norpsilocin according to claim 8 a kind of, which is characterized in that the step
In rapid 2, it is described be added Ethyl formate when reaction time be 10~20h；It is described be added reducing agent when reaction time be 1~
3h。
10. according to a kind of preparation method of natural products Norpsilocin described in any one of claim 1-9, feature
It is, in the step 2, the reducing agent is at least one of lithium aluminium hydride reduction, sodium borohydride.
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| EP3934633A4 (en) * | 2019-03-07 | 2023-03-29 | Arbormentis LLC | Compositions and methods of use comprising substances with neural plasticity actions administered at non-psychedelic/psychotomimetic dosages and formulations |
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Cited By (2)
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| EP3934633A4 (en) * | 2019-03-07 | 2023-03-29 | Arbormentis LLC | Compositions and methods of use comprising substances with neural plasticity actions administered at non-psychedelic/psychotomimetic dosages and formulations |
| CN112300050A (en) * | 2020-11-20 | 2021-02-02 | 保定保利瑞合生物科技有限公司 | Method for preparing N-methyl-5-hydroxytryptamine by taking 5-hydroxytryptamine hydrochloride as raw material |
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