CN108314641B - Preparation method of natural product Norpsilocin - Google Patents
Preparation method of natural product Norpsilocin Download PDFInfo
- Publication number
- CN108314641B CN108314641B CN201711448672.9A CN201711448672A CN108314641B CN 108314641 B CN108314641 B CN 108314641B CN 201711448672 A CN201711448672 A CN 201711448672A CN 108314641 B CN108314641 B CN 108314641B
- Authority
- CN
- China
- Prior art keywords
- mixed solution
- norpsilocin
- iodine
- reaction
- acetic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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 preparation method of a natural product Norpsilocin, which is realized by the following steps: 1) dissolving tryptamine in an organic mixed solution, cooling to-10-0 ℃, dropwise adding the iodine-containing organic mixed solution while stirring, heating to room temperature after dropwise adding for reaction, and then quenching, extracting, drying and concentrating to obtain an intermediate product; 2) and dissolving the intermediate product in an organic solvent, heating, adding ethyl formate while stirring, cooling the system to-10-0 ℃ after the reaction is finished, adding a reducing agent to continue the reaction, and then quenching, extracting, drying, concentrating and separating by column chromatography to obtain the natural product Norpsilocin. According to the invention, commercial and easily available tryptamine and ethyl formate are used as starting raw materials, and the Norpsilocin is synthesized under the catalysis of bismuth acetate, cuprous chloride and a reducing agent (lithium aluminum hydride), so that the preparation method is simple, the operation steps are reduced, and the synthesis cost is low; convenient separation, high yield and good selectivity.
Description
Technical Field
The invention belongs to the technical field of natural product synthesis, and relates to a preparation method of a natural product Norpsilocin.
Background
Norpsilocin is a novel natural product of indole alkaloid, which is found in the research on Psilocybe cubensis of the mushroom with hallucinogenic toxicity phoma lid by the German Dirk Hoffmeister subject group; (Claudius Lenz, Jonas Wick, Dirk Hoffmeister, J.Nat.Prod.2017, 80, 2835-. The natural product has the same basic molecular structure as the natural product Baeocystin (Leung AY, Paul AG Journal of Pharmaceutical sciences.1968, 57, 1667-doped 1671.) but no preparation scheme is available for the compound at present; the case provides a simple and practical preparation method for Norpsilocin.
Disclosure of Invention
In view of the above, the present invention aims to provide a method for preparing a natural product Norpsilocin.
In order to achieve the purpose, the technical scheme of the invention is realized as follows: a method for preparing a natural product Norpsilocin, which is realized by the following steps:
step 1, dissolving tryptamine in an organic mixed solution, cooling to-10-0 ℃, dropwise adding an iodine-containing organic mixed solution while stirring, heating to room temperature for reaction after dropwise adding, and then quenching, extracting, drying and concentrating to obtain an intermediate product;
and 2, dissolving the intermediate product obtained in the step 1 in an organic solvent, heating to 90-100 ℃, adding ethyl formate while stirring, cooling the system to-10-0 ℃ after the reaction is finished, adding a reducing agent to continue the reaction, and then quenching, extracting, drying, concentrating and carrying out column chromatography separation to obtain the natural product Norpsilocin.
Preferably, in the step 1, the organic mixed solution is a mixed solution of acetic acid, sodium acetate and water.
Preferably, in the step 1, the molar ratio of the tryptamine to the sodium acetate in the organic mixed solution is 1: (1-2).
Preferably, in the step 1, the specific preparation method of the iodine-containing organic mixed solution is as follows: dissolving iodine in tetrahydrofuran, and adding bismuth acetate, cuprous chloride, acetic acid and water while stirring to obtain an iodine-containing organic mixed solution.
Preferably, in the step 1, the molar ratio of iodine, bismuth acetate and cuprous chloride in the tryptamine and iodine-containing organic mixed solution is 1: (1-1.5): (0.1-0.5): (0.3-0.8).
Preferably, in the step 1, the reaction time is 8-12 h.
Preferably, in the step 2, the molar ratio of the intermediate product to the ethyl formate is 1: (3-5).
Preferably, in the step 2, the organic solvent is Tetrahydrofuran (THF), dichloromethane (CH)2Cl2) And diethyl ether, preferably Tetrahydrofuran (THF).
Preferably, in the step 2, the reaction time when the ethyl formate is added is 10-20 h; the reaction time when the reducing agent is added is 1-3 h.
Preferably, in the step 2, the reducing agent is lithium aluminum hydride (LiAlH)4) Sodium borohydride (NaBH)4) Preferably lithium aluminum hydride (LiAlH 4).
Compared with the prior art, the invention adopts commercially available tryptamine and ethyl formate as starting raw materials, and synthesizes Norpsilocin under the catalysis of bismuth acetate, cuprous chloride and a reducing agent (lithium aluminum hydride), the preparation method is simple, the operation steps are reduced, and the synthesis cost is low; the separation is convenient, the yield is high, the selectivity is good, and the used reagents are common reagents and are cheap and easy to obtain.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The invention provides a preparation method of a natural product Norpsilocin, which has the following reaction equation:
the method is realized by the following steps:
step 1, dissolving tryptamine in an organic mixed solution, cooling to-10-0 ℃, and dropwise adding iodine (I) under stirring2) After dropwise adding, heating to room temperature for reacting for 8-12 h, and then quenching, extracting, drying and concentrating to obtain an intermediate product;
wherein the organic mixed solution is a mixed solution of acetic acid, sodium acetate and water; the molar ratio of the tryptamine to the sodium acetate in the organic mixed solution is 1: (1-2); containing iodine (I)2) The specific preparation method of the organic mixed solution comprises the following steps: mixing iodine (I)2) Dissolving in Tetrahydrofuran (THF), adding bismuth acetate, cuprous chloride, acetic acid and water under stirring to obtain iodine-containing organic mixed solution; iodine (I) in tryptamine and iodine-containing organic mixed solution2) And the molar ratio of the bismuth acetate to the cuprous chloride is 1: (1-1.5): (0.1-0.5): (0.3 to 0.8); adding iodine (I) dropwise2) The speed of (2) is 5-20 drops/min;
step 2, dissolving the intermediate product obtained in the step 1 in an organic solvent, heating to 90-100 ℃, adding ethyl formate to react for 10-20 hours under stirring, cooling the system to-10-0 ℃ after the reaction is finished, adding a reducing agent to continue reacting for 1-3 hours, and then quenching, extracting, drying, concentrating and performing column chromatography separation to obtain a natural product Norpsilocin;
wherein the moles of intermediate product and ethyl formateThe ratio is 1: (3-5); the organic solvent is at least one of tetrahydrofuran, dichloromethane and diethyl ether, preferably Tetrahydrofuran (THF); the reducing agent is lithium aluminum hydride (LiAlH)4) Sodium borohydride (NaBH)4) Preferably lithium aluminum hydride (LiAlH)4)。
Compared with the prior art, the invention adopts commercially available tryptamine and ethyl formate as starting raw materials, and synthesizes Norpsilocin under the catalysis of bismuth acetate, cuprous chloride and a reducing agent (lithium aluminum hydride), the preparation method is simple, the operation steps are reduced, and the synthesis cost is low; the separation is convenient, the yield is high, the selectivity is good, and the used reagents are common reagents and are cheap and easy to obtain.
Example 1
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding a mixed solution of 1.5mol of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to 0 ℃; under the protection of nitrogen, 1mol of iodine (I)2) Placing in an eggplant bottle treated with anhydrous oxygen-free treatment, adding Tetrahydrofuran (THF), stirring, adding 0.3mol of bismuth acetate, 0.5mol of cuprous chloride, acetic acid and water (volume ratio of acetic acid to water is 1:5) to obtain iodine (I)2) The organic mixed solution of (4); at 0 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into (5-20 drops/min) organic solution containing tryptamine at 0 ℃, heating to room temperature for reaction for 10 hours after the dropping is finished, and then, adding saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate product obtained in the step 1 in Tetrahydrofuran (THF), heating to 100 ℃, adding 4mol of ethyl formate while stirring for reaction for 15 hours, cooling the system to 0 ℃ after the reaction is finished, and adding lithium aluminum hydride (LiAlH)4) The reaction was continued for 1h, after which it was quenched with ice water, extracted with ethyl acetate, the organic phase was collected and dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to give the natural product Norpsilocin (yield 91.1%)。
Example 2
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding a mixed solution of 1.5mol of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to-10 ℃; under the protection of nitrogen, 1mol of iodine (I)2) Placing in an eggplant bottle treated with anhydrous oxygen-free treatment, adding Tetrahydrofuran (THF), stirring, adding 0.3mol of bismuth acetate, 0.5mol of cuprous chloride, acetic acid and water (volume ratio of acetic acid to water is 1:5) to obtain iodine (I)2) The organic mixed solution of (4); at-10 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into the tryptamine-containing organic solution at the temperature of between 5 and 20 drops/min and 10 ℃, heating to room temperature for reaction for 12 hours after the dropping is finished, and then, reacting with saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate product obtained in the step 1 in Tetrahydrofuran (THF), heating to 100 ℃, adding 4mol of ethyl formate to react for 10 hours under stirring, cooling the system to-10 ℃ after the reaction is finished, and adding lithium aluminum hydride (LiAlH)4) The reaction was continued for 2h, after which it was quenched with ice water, extracted with ethyl acetate, the organic phase was collected and dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the natural product Norpsilocin (yield 90.6%).
Example 3
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding a mixed solution of 1.5mol of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to 0 ℃; under the protection of nitrogen, 1mol of iodine (I)2) Placing in an eggplant bottle treated with anhydrous oxygen-free treatment, adding Tetrahydrofuran (THF), stirring, adding 0.3mol of bismuth acetate, 0.5mol of cuprous chloride, acetic acid and water (volume ratio of acetic acid to water is 1:5) to obtain iodine (I)2) The organic mixed solution of (4); at 0 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into (5-20 drops/min) organic solution containing tryptamine at 0 ℃, heating to room temperature for reacting for 8 hours after the dropping is finished, and then, using saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate product obtained in the step 1 in Tetrahydrofuran (THF), heating to 100 ℃, adding 4mol of ethyl formate while stirring for reaction for 20 hours, cooling the system to 0 ℃ after the reaction is finished, and adding lithium aluminum hydride (LiAlH)4) The reaction was continued for 3h, after which it was quenched with ice water, extracted with ethyl acetate, the organic phase was collected and dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the natural product Norpsilocin (89.3% yield).
Example 4
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding a mixed solution of 1.5mol of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to 0 ℃; under the protection of nitrogen, 1mol of iodine (I)2) Placing in an eggplant bottle treated with anhydrous oxygen-free treatment, adding Tetrahydrofuran (THF), stirring, adding 0.3mol of bismuth acetate, 0.5mol of cuprous chloride, acetic acid and water (volume ratio of acetic acid to water is 1:5) to obtain iodine (I)2) The organic mixed solution of (4); at 0 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into (5-20 drops/min) organic solution containing tryptamine at 0 ℃, heating to room temperature for reaction for 12 hours after the dropping is finished, and then, adding saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate product obtained in the step 1 in Tetrahydrofuran (THF), heating to 100 ℃, adding 4mol of ethyl formate to react for 10 hours under stirring, cooling the system to 0 ℃ after the reaction is finished, and adding lithium aluminum hydride (LiAlH)4) Continuing the reaction for 2h, then quenching the reaction product with ice water, extracting the reaction product with ethyl acetate, and collecting an organic phaseDried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain Norpsilocin (yield 90.7%) as a natural product.
Example 5
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding a mixed solution of 1mol of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to 0 ℃; under the protection of nitrogen, 1.2mol of iodine (I)2) Placing in an eggplant bottle treated with anhydrous oxygen-free treatment, adding Tetrahydrofuran (THF), stirring, adding 0.1mol of bismuth acetate, 0.3mol of cuprous chloride, acetic acid and water (volume ratio of acetic acid to water is 1:5) to obtain iodine (I)2) The organic mixed solution of (4); at 0 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into (5-20 drops/min) organic solution containing tryptamine at 0 ℃, heating to room temperature for reaction for 10 hours after the dropping is finished, and then, adding saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate product obtained in the step 1 in Tetrahydrofuran (THF), heating to 100 ℃, adding 3mol of ethyl formate while stirring for reaction for 15 hours, cooling the system to 0 ℃ after the reaction is finished, and adding lithium aluminum hydride (LiAlH)4) The reaction was continued for 1h, after which it was quenched with ice water, extracted with ethyl acetate, the organic phase was collected and dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the natural product Norpsilocin (yield 90.2%).
Example 6
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding a mixed solution of 1mol of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to-10 ℃; under the protection of nitrogen, 1.2mol of iodine (I)2) Placing in an eggplant bottle treated in anhydrous oxygen-free condition, adding Tetrahydrofuran (THF), stirring, adding 0.1mol of bismuth acetate, 0.3mol of cuprous chloride, acetic acid and water (volume ratio of acetic acid to water is 1:5)) Is prepared from iodine (I)2) The organic mixed solution of (4); at-10 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into the tryptamine-containing organic solution at the temperature of between 5 and 20 drops/min and 10 ℃, heating to room temperature for reaction for 12 hours after the dropping is finished, and then, reacting with saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate product obtained in the step 1 in Tetrahydrofuran (THF), heating to 100 ℃, adding 3mol of ethyl formate to react for 10 hours under stirring, cooling the system to-10 ℃ after the reaction is finished, and adding lithium aluminum hydride (LiAlH)4) The reaction was continued for 2h, after which it was quenched with ice water, extracted with ethyl acetate, the organic phase was collected and dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to give the natural product Norpsilocin (88.4% yield).
Example 7
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding a mixed solution of 1mol of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to 0 ℃; under the protection of nitrogen, 1.2mol of iodine (I)2) Placing in an eggplant bottle treated with anhydrous oxygen-free treatment, adding Tetrahydrofuran (THF), stirring, adding 0.1mol of bismuth acetate, 0.3mol of cuprous chloride, acetic acid and water (volume ratio of acetic acid to water is 1:5) to obtain iodine (I)2) The organic mixed solution of (4); at 0 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into (5-20 drops/min) organic solution containing tryptamine at 0 ℃, heating to room temperature for reacting for 8 hours after the dropping is finished, and then, using saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate product obtained in the step 1 in Tetrahydrofuran (THF), heating to 100 ℃, adding 3mol of ethyl formate while stirring for reaction for 20 hours, cooling the system to 0 ℃ after the reaction is finished, and adding lithium aluminum hydride(LiAlH4) The reaction was continued for 3h, after which it was quenched with ice water, extracted with ethyl acetate, the organic phase was collected and dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the natural product Norpsilocin (yield 86.5%).
Example 8
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding a mixed solution of 1mol of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to 0 ℃; under the protection of nitrogen, 1.2mol of iodine (I)2) Placing in an eggplant bottle treated with anhydrous oxygen-free treatment, adding Tetrahydrofuran (THF), stirring, adding 0.1mol of bismuth acetate, 0.3mol of cuprous chloride, acetic acid and water (volume ratio of acetic acid to water is 1:5) to obtain iodine (I)2) The organic mixed solution of (4); at 0 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into (5-20 drops/min) organic solution containing tryptamine at 0 ℃, heating to room temperature for reaction for 12 hours after the dropping is finished, and then, adding saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate product obtained in the step 1 in Tetrahydrofuran (THF), heating to 100 ℃, adding 3mol of ethyl formate to react for 10 hours under stirring, cooling the system to 0 ℃ after the reaction is finished, and adding lithium aluminum hydride (LiAlH)4) The reaction was continued for 2h, after which it was quenched with ice water, extracted with ethyl acetate, the organic phase was collected and dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to give the natural product Norpsilocin (87.2% yield).
Example 9
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding 2mol of mixed solution of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to 0 ℃; under the protection of nitrogen, 1.5mol of iodine (I)2) Placing in an eggplant bottle treated in anhydrous oxygen-free condition, adding Tetrahydrofuran (THF), stirring,then 0.5mol of bismuth acetate, 0.8mol of cuprous chloride, acetic acid and water (the volume ratio of acetic acid to water is 1:5) are added to prepare the iodine (I)2) The organic mixed solution of (4); at 0 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into (5-20 drops/min) organic solution containing tryptamine at 0 ℃, heating to room temperature for reaction for 10 hours after the dropping is finished, and then, adding saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate product obtained in the step 1 in Tetrahydrofuran (THF), heating to 100 ℃, adding 5mol of ethyl formate while stirring for reaction for 15 hours, cooling the system to 0 ℃ after the reaction is finished, and adding lithium aluminum hydride (LiAlH)4) The reaction was continued for 1h, after which it was quenched with ice water, extracted with ethyl acetate, the organic phase was collected and dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the natural product Norpsilocin (89.7% yield).
Example 10
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding 2mol of mixed solution of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to-10 ℃; under the protection of nitrogen, 1.5mol of iodine (I)2) Placing in an eggplant bottle treated with anhydrous oxygen-free treatment, adding Tetrahydrofuran (THF), stirring, adding 0.5mol of bismuth acetate, 0.8mol of cuprous chloride, acetic acid and water (volume ratio of acetic acid to water is 1:5) to obtain iodine (I)2) The organic mixed solution of (4); at-10 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into the tryptamine-containing organic solution at the temperature of between 5 and 20 drops/min and 10 ℃, heating to room temperature for reaction for 12 hours after the dropping is finished, and then, reacting with saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate obtained in step 1 in Tetrahydrofuran (THF), heating to 100 deg.C, and adding while stirringAdding 5mol of ethyl formate to react for 10 hours, cooling the system to-10 ℃ after the reaction is finished, and adding lithium aluminum hydride (LiAlH)4) The reaction was continued for 2h, after which it was quenched with ice water, extracted with ethyl acetate, the organic phase was collected and dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to give the natural product Norpsilocin (87.4% yield).
Example 11
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding 2mol of mixed solution of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to 0 ℃; under the protection of nitrogen, 1.5mol of iodine (I)2) Placing in an eggplant bottle treated with anhydrous oxygen-free treatment, adding Tetrahydrofuran (THF), stirring, adding 0.5mol of bismuth acetate, 0.8mol of cuprous chloride, acetic acid and water (volume ratio of acetic acid to water is 1:5) to obtain iodine (I)2) The organic mixed solution of (4); at 0 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into (5-20 drops/min) organic solution containing tryptamine at 0 ℃, heating to room temperature for reacting for 8 hours after the dropping is finished, and then, using saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate product obtained in the step 1 in Tetrahydrofuran (THF), heating to 100 ℃, adding 5mol of ethyl formate while stirring for reaction for 20 hours, cooling the system to 0 ℃ after the reaction is finished, and adding lithium aluminum hydride (LiAlH)4) The reaction was continued for 3h, after which it was quenched with ice water, extracted with ethyl acetate, the organic phase was collected and dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the natural product Norpsilocin (yield 90.5%).
Example 12
Step 1, under the protection of nitrogen, putting 1mol of tryptamine into an eggplant bottle which is treated in an anhydrous and oxygen-free way, adding 2mol of mixed solution of sodium acetate, acetic acid and water (the volume ratio of the acetic acid to the water is 1:5) to prepare an organic mixed solution containing tryptamine, and cooling to 0 ℃; under the protection of nitrogen, 1 is carried out.5mol of iodine (I)2) Placing in an eggplant bottle treated with anhydrous oxygen-free treatment, adding Tetrahydrofuran (THF), stirring, adding 0.5mol of bismuth acetate, 0.8mol of cuprous chloride, acetic acid and water (volume ratio of acetic acid to water is 1:5) to obtain iodine (I)2) The organic mixed solution of (4); at 0 deg.C, adding iodine (I)2) Slowly dropping the organic mixed solution into (5-20 drops/min) organic solution containing tryptamine at 0 ℃, heating to room temperature for reaction for 12 hours after the dropping is finished, and then, adding saturated K2CO3Quenching the aqueous solution, extracting with ethyl acetate, collecting the organic phase, drying with anhydrous sodium sulfate, and concentrating to obtain intermediate product;
step 2, dissolving 1mol of the intermediate product obtained in the step 1 in Tetrahydrofuran (THF), heating to 100 ℃, adding 5mol of ethyl formate to react for 10 hours under stirring, cooling the system to 0 ℃ after the reaction is finished, and adding lithium aluminum hydride (LiAlH)4) The reaction was continued for 2h, after which it was quenched with ice water, extracted with ethyl acetate, the organic phase was collected and dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to give the natural product Norpsilocin (89.5% yield).
The spectrogram detection results and analysis are as follows:
performing nuclear magnetic resonance detection on the product obtained in example 1, wherein the specific detection data obtained by the hydrogen spectrogram of the product obtained in example 1 are as follows:1H NMR(CD3OD，400MHz)：＝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, 400 MHz): 153.0, 141.3, 124.3, 123.4, 118.2, 110.7, 105.0, 104.4, 52.8, 34.0, 25.4 through detection data, it can be seen that the natural product Norpsilocin prepared by the method has stable H atom peak position in different chemical environments, no impurity peak, high purity, good separability and high yield.
Since the detection data of the product obtained in any of examples 2 to 12 is the same as that of the product obtained in example 1, the data analysis of the product obtained in any of examples 2 to 12 was not performed.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the scope of the present invention.
Claims (6)
1. A preparation method of a natural product Norpsilocin is characterized by comprising the following steps:
dissolving tryptamine in an organic mixed solution of acetic acid, sodium acetate and water, cooling to-10-0 ℃, dropwise adding a mixed solution of tetrahydrofuran, acetic acid, cuprous chloride, bismuth acetate and water containing iodine simple substances while stirring, heating to room temperature for reaction after dropwise adding, and then quenching, extracting, drying and concentrating to obtain an intermediate product;
step 2, dissolving the intermediate product obtained in the step 1 in tetrahydrofuran, heating to 90-100 ℃, adding ethyl formate while stirring, cooling the system to-10-0 ℃ after the reaction is finished, adding a lithium aluminum hydride reducing agent to continue the reaction, and then quenching, extracting, drying, concentrating and separating by column chromatography to obtain a natural product Norpsilocin;
in the step 1, the molar ratio of the tryptamine to the acetic acid, the sodium acetate and the sodium acetate in the water mixed solution is 1: (1-2).
2. The method for preparing the natural product Norpsilocin according to claim 1, wherein the iodine-containing mixed solution is prepared by the following steps in step 1: dissolving iodine in tetrahydrofuran, and adding bismuth acetate, cuprous chloride, acetic acid and water while stirring to obtain an iodine-containing organic mixed solution.
3. The method for preparing a natural product Norpsilocin according to claim 2, wherein in the step 1, the molar ratio of iodine, bismuth acetate and cuprous chloride in the mixed solution of tryptamine and iodine is 1: (1-1.5): (0.1-0.5): (0.3-0.8).
4. The method for preparing a natural product Norpsilocin according to claim 3, wherein the reaction time in step 1 is 8-12 h.
5. The method for preparing a natural product Norpsilocin according to claim 4, wherein the molar ratio of the intermediate product to the ethyl formate in the step 2 is 1: (3-5).
6. The method for preparing the Norpsilocin of claim 5, wherein in the step 2, the reaction time for adding the ethyl formate is 10-20 h; the reaction time when the reducing agent is added is 1-3 h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711448672.9A CN108314641B (en) | 2017-12-27 | 2017-12-27 | Preparation method of natural product Norpsilocin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711448672.9A CN108314641B (en) | 2017-12-27 | 2017-12-27 | Preparation method of natural product Norpsilocin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108314641A CN108314641A (en) | 2018-07-24 |
| CN108314641B true CN108314641B (en) | 2020-11-13 |
Family
ID=62893432
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711448672.9A Active CN108314641B (en) | 2017-12-27 | 2017-12-27 | Preparation method of natural product Norpsilocin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108314641B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2021010753A (en) * | 2019-03-07 | 2021-12-15 | Arbormentis LLC | Compositions and methods of use comprising substances with neural plasticity actions administered at non-psychedelic/psychotomimet ic 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 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1268484A1 (en) * | 2000-03-17 | 2003-01-02 | Novo Nordisk A/S | Condensed imidazoles as histamine h3 receptor ligands |
| US6437147B1 (en) * | 2000-03-17 | 2002-08-20 | Novo Nordisk | Imidazole compounds |
-
2017
- 2017-12-27 CN CN201711448672.9A patent/CN108314641B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN108314641A (en) | 2018-07-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103694469A (en) | Sulfide functionalized covalent organic frame material and synthesis method thereof | |
| CN106902880B (en) | 4,6- dimethyl -2- mercaptopyrimidine univalent copper complex prepares the application in alcohol in catalysis ketone or aldehyde hydrogen transfer reaction | |
| CN108314641B (en) | Preparation method of natural product Norpsilocin | |
| CN112376076B (en) | Preparation method of azoxybenzene | |
| CN111620808B (en) | 2-aldehyde indole compound and preparation method thereof | |
| CN107629051B (en) | Method for synthesizing evodiamine by carbonylation reaction three-step method | |
| CN102382096A (en) | Method for preparing isocoumarin and derivatives thereof | |
| CN107880063B (en) | A kind of synthetic method of dauricine | |
| CN102382038B (en) | Preparation method for synthesizing carbazoles alkaloid Siamenol | |
| CN103467449B (en) | Piperidine derivative, and preparation method and application thereof in preparation of halofuginone | |
| CN110498744A (en) | A kind of preparation method of 1- ethyl -3- nitrobenzene | |
| CN110734354B (en) | Method for preparing biaryl compound from alcohol compound | |
| CN111138269B (en) | Process method for preparing 2-butanone acid sodium salt | |
| CN110283040B (en) | Synthetic method of 3-methyl-D3-benzyl bromide | |
| CN103497138A (en) | Method of preparing cis-octahydroisoindole by zinc chloride and potassium borohydride | |
| CN112125864B (en) | Synthesis method of 1,1 '-diamino-5, 5' -bitetrazole | |
| CN105130841A (en) | Preparation method of 3-iodophenyl azide compound | |
| CN112609202A (en) | Method for synthesizing natural product Xanthoisozoline B through electrocatalysis and product thereof | |
| CN111747923A (en) | Crown ether carboxylic acid compound-containing BPDC-12-C-4 and preparation method and application thereof | |
| CN109305968B (en) | A kind of preparation method of stable isotope labeling 6-benzyladenine internal standard reagent | |
| CN107652274B (en) | Pentaerythritol immobilized (S) or (R) -diphenyl prolinol, and preparation method and application thereof | |
| CN103936753B (en) | Natural products Daldinin and the like total synthesis method | |
| CN110105371B (en) | Impurities in doladazole bulk drug and preparation method thereof | |
| CN103508999A (en) | Maxacalcitol synthesizing intermediate and preparation method and application thereof | |
| CN109942590B (en) | Preparation method of nitidine chloride |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |