Synthesis method of optically-active beta-amino ketones

Abstract

The invention discloses a synthesis method of optically-active beta-amino ketones represented by formula (I). The synthesis method is characterized in that benzothiazole imide represented by formula (II) and aromatic ketone compounds represented by formula (III) undergo an asymmetric Mannich reaction under the action of a cinchona-derived quaternary ammonium salt phase transfer catalyst represented by formula (IV) in a reaction medium composed of an organic solvent and an aqueous alkali solution to obtain the optically-active beta-amino ketones represented by formula (I). The synthesis methodhas the advantages of mild reaction conditions, simplicity in operation, good substrate adaptability and high atom utilization rate.

Description

technical field [0001] The invention relates to a synthetic method of an optically active β-aminoketone compound. Background technique [0002] β-amino ketones are not only important drugs and synthetic intermediates of natural products (such as β-lactams, β-amino alcohols, β-amino acids, etc.) (Tramontini M., et al., Tetrahedron, 1990,46( 6), 1791.) and it also has a wide range of biological activities such as anti-inflammatory, anti-cancer, anti-tuberculosis, antibacterial, and pain relief. β-Aminoketones with anti-inflammatory effects a (Chen H.T., et al., Acta. Pharm. Sin., 1991, 26 (3), 183.) and b (Gevorgyan G.A., et al., Chem. inform. , 2003, 34(30), 152.). [0003] [0004] Reported β-aminoketone compounds with antibacterial activity c (Joshi S., et al., Bioorg. Med. Chem. Lett., 2007, 17 (3), 645.) and d (Damljanovi I., et al ., J. Orgmetal. Chem., 2011, 696(23), 3703.). [0005] [0006] Reported β-amino ketones with anti-tuberculosis activity (Das U., et...

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Problems solved by technology

[0011] The synthetic method of non-optically active β-aminoketone has: protonic acid is used as catalyst method (Yi L., et al., Synthesis., 1991,717, 2); Lewis acid is used as catalyst method (Yang Y.Y., et al., Tetrahedron,2006,62,10079.); Ionic liquid as catalyst method (Hao G.Y., et al., Green Chem.,2004,6,75.) Solid acid as catalyst method (Azizi N., et al., Org. Lett., 2006,8 (10): 2079.), iodine simple substance is used as catalyst method (Meng Tuanjie et al. Journal of Shangqiu Normal University, 2006, 22 (2): 101), this series of methods has complex post-processing and low reaction yield not high disadvantage

[0012] At present, optically active β-amino ketones can be obtained mainly through chiral resolution (CN1065265), directional synthesis (synthesis of chiral raw materials), enzymatic catalysis, asymmetric catalysis and other methods; Low economy, waste of raw materials; disadvantages of directional synthesis (synthesis of chiral raw materials): there are relatively few things that can be synthesized by this method, that is, it is difficult to find corresponding latent chiral raw materials; disadvantages of enzyme catalysis: it is difficult to choose enzymes or strains , it is difficult to identify, the conditions are not easy to control, the enzyme or strain is not easy to preserve, easy to inactivate, the reaction solution is often viscous, the post-treatment is not easy to carry out and the reaction yield is not high

So far, there has been no report of "the study on the asymmetric Mannich reaction of benzothiazolimine and aromatic ketones catalyzed by the quaternary ammonium bromide salt derived from cinchona base as a phase transfer catalyst". β-Amino ketones are of great importance

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