Acronine

Acronine Chemische Eigenschaften,Einsatz,Produktion Methoden

• Originator

  Acronine ,ZYF Pharm Chemical

• Verwenden

  Antineoplastic.

• Definition

  ChEBI: An alkaloid antineoplastic agent isolated from Acronychia baueri.

• Manufacturing Process

  The acridone alkaloids constitute a small group of natural products found exclusively in the Rutaceae family of higher plants. A sustained interest in this field has been due to the reported activity of acronycine a constituent of Acronnychia baueri and Vepris amphody as an anti-tumor agent.
  There are different methods of the synthetic preparation of acronycine (W. M. Bandaranayake et al., J. Chem. Soc. Perkin 1, 998 (1968); J. Hlubucek et al.; Aust. J. Chem. 23, 1881 (1970). One of them is described below. Friedel- Crafts condensation between 2-nitrobenzoyl chloride and 3,5- dimethoxyphenol.
  2-Nitrobenzoyl chloride (12 g) and AlCl3, (anhyd., 13 g) were dissolved in dry ether (50 ml) and this mixture added to a solution of 3.5-dimethoxyphenol (5 g) in dry ether 150 ml) at 0°C and the final mixture stirred at 0°C for 3 hours, brought to 20°C and stirred for a further 3 h. Diluted HCl and ice were added and the product extracted with EtOAc (3x50 ml), this extract was washed with aq. NaHCO3, water, dried (MgSO4), filtered and evaporated under reduced pressure to yield a dark red oil. This oil was treated with 2 M aq. NaOH. (100 ml) for 1 h., acidified with diluted HCl and re-extracted with EtOAc which gave, after a similar work up, a paled red oil (5.0 g). Thin layer chromatography (TLC) showed three components one of which was the starting phenol. Column chromatography (150 g silica gel) and elution with benzene:petrol ether 40°-60°C (1:1) followed by increasing polarity of solvents (benzene through chloroform to chloroform:ether (4:1) gave 59 fractions. Fractions 1-12 were combined to gave a solid, which crystallized from benzene to give 4,6-dimethoxy-2-hydroxy-2-nitrobenzophenone, MP: 198°-199°C. Fractions 13-21 were discarded. Fractions 22-42 were combined (0.3 g), crystallized from benzene and the product added to that obtained from fractions 43-59 which crystallized from benzene to give 2,6-dimethoxy- 7-hydroxy-2-nitrobenzophenone (0.5 g) MP: 175°-177°C. Condensation of 3-chloro-3-methylbutyne with 2,6-dimethoxy-7-hydroxy-2- nitrobenzophenone:
  A solution of the above benzophenone (2 g) and excess 3-chloro-3- methylbutyne (4.5 g) in dry DMF (60 ml) containing anhydrous K2CO3 (4 g) and dry KI (2 g) was stirred and heated at 65°C for 14 hours (under N2). The mixture was cooled, diluted with water, acidified, extracted with chloroform (3x50 ml) and the extract was worked up in the usual way (including a NaOH wash) to give an oil, which was redissolved in DMF (20 ml) and heated at 130°C, under N2, for 7 h whence most of the starting material had disappeared. The solvent was removed under reduced pressure to give a product (0.62 g) which was purified by preparative layer chromatography on silica gel to give 6-(2-nitrobehzoyl)-5,7-dimethoxy-2,2-dimethylchromene (0.22 g) which crystallized from EtOH, MP: 92°-93°C.
  6-(2-Aminobenzoyl)-5,7-dimethoxy-2,2-dimethylchromene (0.2 g) was dissolved in EtOH (30 ml) containing water (5 ml) and ammonium chloride (1 g) and Zn mossy (1.5 g) was added in portions and the mixture stirred at room temperature for 5 days. The solution was filtered, evaporated to dryness under reduced pressure and the residue dissolved in EtOAc (25 ml) and worked up in the usual way to give a solid (0.19 g). It crystallised from EtOH with MP: 123°-126°C.
  Cyclization of aminodimethylchromenylbenzophenone: 6-(2-aminobenzoyl)- 5,7-dimethoxy-2,2-dimethylchromene (0.12 g) was dissolved in DMSO (8 ml) and NaH (0.06 g) added, the mixture was stirred for 6 days at room temperature. A further addition of NaH (0.06 g) was made and the solution heated to 50°C for 0.5 h whence it was poured into water, extracted with EtOAc and worked up in the usual way to give a crude mixture (0.11 g; components). Separation of this mixture on plate (silica gel:benzene:EtOAc, 10:4) gave band 1 (Rf 0.45: 38 mg) identified as starting material. Band 2 (Rf 0.32: 42 mg; 43%) which crystallized from ethylacetate as des-Nmethyl

• Therapeutic Function

  Antineoplastic

• Allgemeine Beschreibung

  Yellow powder.

• Air & Water Reaktionen

  Water insoluble.

• Reaktivität anzeigen

  Amines, like Acronine, are weak chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.

• Health Hazard

  ACUTE/CHRONIC HAZARDS: When heated to decomposition Acronine emits toxic fumes.

• Brandgefahr

  Flash point data for Acronine are not available. Acronine is probably combustible.

Acronine Upstream-Materialien And Downstream Produkte

Acronine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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