Structure And Antibacterial Activity Of Modified Macleaya Gyrus And Benzo Protopine Alkaloids Of Coffee

Macleaya cordata (Willd) R. Br. is a species from genus Papaveraceae, Macleaya plants. This plant widely distributed in the middle and lower reaches of Yangtze river basin region. The main active constituents of Macleaya cordata are benzylisoquinoline alkaloids. It has antimicrobial, anti-inflammatory and insecticidal activity. Various types of isoquinoline alakaloids are involved in the biosynthesis of quaternary benzo[c]phenanthridine alkaloids. Many of the biosynthetic precursors are never isolated from Macleaya cordata. In order to study the structure-activity relationship(SAR) of these biosynthetic intermediates, the structure of four alkaloids(protopine, allocryptopine, sanguinarine, chelerythrine) are modified in this article. A series of isoquinoline derivatives were got and evaluated for their antibacterial activities, then the structure-activity relationship(SAR) of these compounds is discussed in this paper.1. structure modification of protopine, allocryptopine, sanguinarine, chelerythrine:(1). Reaction of protopine or allocryptopine with oxalyl chloride provided the N-methy-13,14-dehydroprotoberberine quaternary salts. A DMSO solution of N-methy-13,14-dehydroprotoberberine quaternary salts was heated at120℃to yield protoberberine salts. Protoberberine salts were reduced by NaBH4to yield tetrahydroprotoberberine alkaloids. Allocryptopine was reduced by NaBH4to yield hydroxyl derivative. Reaction of hydroxyl derivative with CF3COOH afforded N-methyl canadine salts.(2). Reduction of sanguinarine or chelerythrine via NaBH4obtained dihydrosanguinarine and dihydrochelerythrine. Reaction of sanguinarine or chelerythrine with Grignard reagent CH3MgBr yielded6-methyl dihydrosanguinarine and6-methyl dihydrochelerythrine.6-methyl dihydrosanguinarine and6-methyl dihydrochelerythrine were oxidized by DDQ to provide6-methyl sanguinarine and6-methyl chelerythrine. Reaction of sanguinarine or chelerythrine with K3Fe(CN)6afforded6-oxysanguinarine and6-oxychelerythrine. Getting20compounds include sixteen derivatives and four starting compounds.2. structural analysis of the20compounds:The structures of the20compounds were identified by means of’H-NMR,13C-NMR, ESI-MS, and its NMR signals have been assigned. We also draw the structural formulas of the20compounds.3. the in vitro antibacterial test of the20compounds:The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the20compounds for E. coli, S. aureus, A. staphylocosis, S. choleraesuis were tested by tube serial dilution method. The results show that the four starting compounds (protopine, allocryptopine, sanguinarine, chelerythrine) have good antibacterial activity and the in vitro antibacterial activity of compound7is significantly increased. For the first time found that N-methyl canadine salts with antibacterial activity.The preliminary structure-activity relationship (SAR) indicated that planar molecule structure with high aromatization level or a positive charge of the molecules generates positive influence on the antibacterial activities of these tetracyclic isoquinoline alkaloids.