Studies On Synthesis, Antimicrobial Activity Of 9-O-acyl-substituted Palmatine Analogues And Synthesis Of Caffeine Analogues

Palmatine is an important active component of the common fibraurea stem, and it belongs to the isoquinoline alkaloids. Palmatine has broad spectrum of biological activity, such as antimicrobial, antiviral, antitumor, hypotensive, protection of myocardial infarction, enhancing the immune, hypoglycemic, antioxidant, antiarrhythmic, sedation and liver activities, etc. At the same time, it has been used to treat various inflammations, such as bacillary dysentery, enteritis, surgical infection, gynecological inflammation, pink eye, respiratory tract and urinary tract infection, etc. Palmatine has the rich biological activities, but it is largely limited in clinical application because of its poor fat-solubility and low oral bioavailability. It has been hot topics to develop new active substances by appropriate structural modification of palmatine. The methods and results are as follows.Using Palmatine as raw material, 9-O-acyl-substituted palmatine analogues with a series of different length of acyl chains were synthesized through two steps, and the different reaction conditions on the influence of product yields were studied to optimize the synthetic process. The structure of 9-O-acyl-substituted palmatine analogues synthesized was affirmed with MS, 1H NMR and 13 C NMR.The antimicrobial activities of 9-O-acylpalmatine analogues were investigated by oxford cup method and 2-fold serial dilution test. The microorganisms used for the antimicrobial assay are Gram-positive(G+) bacteria, Staphylococcus aureus, Staphylococcus citreus, Enterococcus faecalis, Micrococcus luteus, and Gram-negative(G-) bacteria, Escherichia coli Ⅰ, Escherichia coli Ⅱ, Proteusbacillus vulgaris, respectively. The results showed that G+ bacteria were sensitive than G- bacteria. The antimicrobial activity increased as the length of aliphatic chain elongated and then decreased gradually when the acyl chain exceeded 12 carbon atoms, and 9-O-dodecanoyl-palmatine derivative show a good antimicrobial activity. Finally, the structure-activity relationships of compounds were discussed.The orthogonal experiment of five factors and four levels was designed to gain the best synthetic conditions of 9-O-n-decanoyl palmatine. The results show that the reaction temperature had a significant impact on the reaction.Caffeine, a kind of alkaloid, is extracted from tea and the fruit of coffee. It is often used in the treatment of neurasthenia and coma recovery, and is closely related to human health. Caffeine has been widely concerned because of the important application value for scientific research. In the work described here, a series of caffeine analogues were synthesized by the reaction of theophylline and halogenated hydrocarbon. The raw materials are provided for further research. The new substances are got by the structural modification of caffeine analogues. The structure of the analogues synthesized was affirmed with MS, 1H NMR and 13 C NMR.