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CN-122010819-A - Synthesis method of cytochalasin natural product curtachalasin B

CN122010819ACN 122010819 ACN122010819 ACN 122010819ACN-122010819-A

Abstract

The invention discloses a synthesis method of cytochalasin compounds curtachalasin B, which comprises the steps of reacting compound 22 with dimethyl ketone peroxide in a solvent at-35 to-20 ℃ to generate a compound 23, reacting compound 23 with boron trifluoride diethyl ether in the solvent at-78 to 5 ℃ to obtain a compound 24, reacting compound 24 with vanadyl acetylacetonate and tert-butyl hydroperoxide in the solvent at 15 to 35 ℃ to obtain a compound 25, dissolving compound 25 in toluene, adding trifluorophenyl boron at room temperature, heating to 80 ℃ to obtain a compound 26, dissolving compound 26 in anhydrous methanol, adding anhydrous potassium carbonate at 0 to 35 ℃, and reacting at room temperature to obtain curtachalasin B. The method has the advantages of simple operation, simple post-treatment, low cost of product separation and purification, high synthesis efficiency, low cost and no special treatment, and the used reagents are mostly obtained commercially.

Inventors

  • DENG JUN
  • GAO FENG

Assignees

  • 南开大学

Dates

Publication Date
20260512
Application Date
20260123

Claims (10)

  1. 1. A method for synthesizing cytochalasin compound curtachalasin B, comprising the steps of: S1, dissolving a compound 22 in acetone, adding dimethyl ketone peroxide at the temperature of minus 35 to minus 20 ℃, reacting for 1.5 to 4 hours at the temperature, quenching the reaction, extracting, merging organic phases, drying, decompressing and filtering, decompressing and concentrating under vacuum to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain a compound 23; S2, dissolving the compound 23 in dichloromethane, adding boron trifluoride diethyl etherate at the temperature of-78-5 ℃, reacting for 2-10 hours at the temperature, extracting, merging organic phases, drying, filtering under reduced pressure, concentrating under reduced pressure under vacuum to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain a compound 24; S3, dissolving the compound 24 in dichloromethane, sequentially adding vanadyl acetylacetonate and tert-butyl hydroperoxide at 15-35 ℃, reacting for 3-12 hours, quenching the reaction, extracting, merging organic phases, drying, filtering under reduced pressure, concentrating under vacuum and decompressing to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain a compound 25; S4, dissolving the compound 25 in toluene, adding the trifluorophenyl boron at room temperature, then heating to 80 ℃, reacting for 4-7 hours, cooling to room temperature, concentrating under vacuum and reducing pressure to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain a compound 26; S5, dissolving the compound 26 in absolute methanol, adding absolute potassium carbonate at 0-35 ℃, then reacting for 10-40 minutes at room temperature, quenching the reaction, extracting, combining organic phases, drying with absolute sodium sulfate, filtering under reduced pressure, concentrating under reduced pressure in vacuum to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain curtachalasin B.
  2. 2. The method according to claim 1, wherein in S1, the concentration of the compound 22 in acetone is 0.02 to 0.2mol/L, and the equivalent ratio of the dimethyl ketone peroxide to the compound 22 is (2.0 to 6.0): 1.
  3. 3. The synthesis method according to claim 1, wherein S1 is a quenching reaction by adding saturated sodium thiosulfate solution into the system for 5-10 minutes, extracting with ethyl acetate, and drying with anhydrous sodium sulfate.
  4. 4. The synthesis method according to claim 1, wherein the concentration of the compound 23 in methylene chloride in S2 is 0.02 to 0.3mol/L, and the equivalent ratio of boron trifluoride diethyl ether to the compound 23 is (1.0 to 10.0): 1.
  5. 5. The synthesis method according to claim 1, wherein in S2, saturated sodium bicarbonate solution is added into the system to quench the reaction for 5-10 minutes, ethyl acetate is used for extraction, and anhydrous sodium sulfate is used for drying.
  6. 6. The synthesis method according to claim 1, wherein in S3, the concentration of the compound 24 in methylene dichloride is 0.01-0.2 mol/L, and the equivalent ratio of the vanadyl acetylacetonate, the tert-butyl hydroperoxide and the compound 24 is (0.05-1.0): (2-5): 1.
  7. 7. The synthesis method according to claim 1, wherein in S3, a saturated sodium thiosulfate solution is added into the system to quench the reaction for 5-10 minutes, and the reaction mixture is extracted by ethyl acetate and dried by anhydrous sodium sulfate.
  8. 8. The synthesis method according to claim 1, wherein in S4, the concentration of the compound 25 in toluene is 0.01-0.2 mol/L, and the equivalent ratio of the trifluorophenyl boron to the compound 25 is (0.8-2): 1.
  9. 9. The synthesis method according to claim 1, wherein in S5, the concentration of the compound 26 in anhydrous methanol is 0.01-0.2 mol/L, and the equivalent ratio of the anhydrous potassium carbonate to the compound 26 is (0.5-5.0): 1.
  10. 10. The synthesis method according to claim 1, wherein in S5, saturated sodium bicarbonate solution is added into the system to quench the reaction for 5-10 minutes, ethyl acetate is used for extraction, and anhydrous sodium sulfate is used for drying.

Description

Synthesis method of cytochalasin natural product curtachalasin B Technical Field The invention relates to the technical field of synthetic chemistry, in particular to a method for synthesizing a cytochalasin natural product curtachalasin B. Background Actin cytoskeleton plays a central role in maintaining cell tissue architecture and dynamic regulation, however, small molecule tools capable of selectively modulating actin function remain very limited. Cytochalasins are a large family of natural products with good cell permeability, target actin, and exhibit diverse cytotoxicity and actin damaging activity in mammalian cells. To date, over 500 cytochalasin family members have been identified separately, which are fungal polyketide-non-ribosomal peptide (PKS-NRPS) hybrid metabolites. Such compounds not only possess unique structural features, but also exhibit a wide range of biological activities, including immunomodulation, cytotoxicity and nematicidal effects, and have therefore long attracted attention in the fields of total synthesis and biosynthesis research. Curtachalasin B is a cytochalasin natural product isolated from potato endophytic fungi Xylaria curta E10 and has potential antibacterial activity. However, the efficiency of curtachalasin B obtained by separation is low, and large-scale acquisition is difficult to be used for subsequent modification improvement and research, so that large-scale preparation through rapid and efficient chemical synthesis is an important means for solving the problem. However, the total synthesis route of curtachalasin B is not reported at present, so that the development of a high-efficiency and simple synthesis route is significant. Disclosure of Invention In view of the above, the invention provides a high-efficiency and economical synthesis method of cytochalasin compound curtachalasin B, which has the advantages of low cost, short production period, high production efficiency and the like. In order to achieve the above purpose, the invention adopts the following technical scheme: a method for synthesizing cytochalasin compound curtachalasin B, comprising the steps of: S1, dissolving a compound 22 in acetone, adding dimethyl ketone peroxide at the temperature of minus 35 to minus 20 ℃, reacting for 1.5 to 4 hours at the temperature, quenching the reaction, extracting, merging organic phases, drying, decompressing and filtering, decompressing and concentrating under vacuum to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain a compound 23; S2, dissolving the compound 23 in dichloromethane, adding boron trifluoride diethyl etherate at the temperature of-78-5 ℃, reacting for 2-10 hours at the temperature, extracting, merging organic phases, drying, filtering under reduced pressure, concentrating under reduced pressure under vacuum to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain a compound 24; S3, dissolving the compound 24 in dichloromethane, sequentially adding vanadyl acetylacetonate and tert-butyl hydroperoxide at 15-35 ℃, reacting for 3-12 hours, quenching the reaction, extracting, merging organic phases, drying, filtering under reduced pressure, concentrating under vacuum and decompressing to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain a compound 25; S4, dissolving the compound 25 in toluene, adding the trifluorophenyl boron at room temperature, then heating to 80 ℃, reacting for 4-7 hours, cooling to room temperature, concentrating under vacuum and reducing pressure to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain a compound 26; S5, dissolving the compound 26 in absolute methanol, adding absolute potassium carbonate at 0-35 ℃, then reacting for 10-40 minutes at room temperature, quenching the reaction, extracting, combining organic phases, drying with absolute sodium sulfate, filtering under reduced pressure, concentrating under reduced pressure in vacuum to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain curtachalasin B. Preferably, the concentration of the compound 22 in acetone in the step S1 is 0.02-0.2 mol/L, and the equivalent ratio of the dimethyl ketone peroxide to the compound 22 is (2.0-6.0): 1. Preferably, in the step S1, a saturated sodium thiosulfate solution is added into the system for quenching reaction for 5-10 minutes, ethyl acetate is used for extraction, and anhydrous sodium sulfate is used for drying. Preferably, in the step S2, the concentration of the compound 23 in methylene chloride is 0.02-0.3 mol/L, and the equivalent ratio of the boron trifluoride diethyl ether to the compound 23 is (1.0-10.0): 1. Preferably, in the step S2, saturated sodium bicarbonate solution is added into the system to quench the reaction for 5-10 minutes, ethyl acetate is used for extractio