| Summary: | 碩士 === 國立臺灣大學 === 藥學研究所 === 89 === 英文摘要
I. Studies on the Alkaloids from the Stems of Cryptocarya chinensis (III)
II. Chemical Modification of Protoberberine Alkaloids
Part I
Previous studies on the alkaloids from the leaves, barks and woods of Cryptocarya chinensis (Lauraceae) revealed that they contained various amounts of pavine alkaloids. It was also reported that pavine alkaloids possess anti-arrhythmic activity. To investigate the structure-activity relationship, it was intended in this part of work to separate the major pavine alkaloids for further chemical modification and bioactivity study. Meanwhile minor alkaloids from this source will be further explored.
The EtOH extract of the stems was triturated with acids to give an aqueous fraction containing mixture of base salts which were extracted exhaustively with CHCl3 to give neutral components. The aqueous solution was then basified with NH4OH(aq) to yield total free bases, which were further divided into phenolic and non-phenolic fractions by acid-base partitioning. All fractions were further separated by conventional adsorption chromatography combined with Sephadex LH-20 and PTLC to give eleven compounds belonging to the following structural types : N-methylpavines: (-)-crychine (1), (+)-O-methylcaryachine (2), (-)-neocaryachine (3), (-)-caryachine (4), (-)-argemonine (5), (-)-12-hydroxy-O-methylcaryachine (6), (-)-6-hydroxycrychine (7); Benzylisoquinoline: (±)-romneine (8); Proaporphine : 10-dehydrocryprochine (9); Pavine N-oxide: (-)-crychine N-oxide (10) and (+)-O-methylcaryachine N-oxide (11).
Among these alkaloids, compound 5 and 10 are known natural compounds, however, they are the first isolated from C. chinensis. Compound 9 is a new natural product, although it had been prepared previously from (+)-cryprochine. Compound 6, 7, 11 are new pavine alkaloids of these, compound 11 is a mixture composed of two inseperable stereo isomers. Their identities were confirmed by chemical correlation.
Part II
Previous studies demonstrated that 8-oxo-berberine possesses positive inotropic and negative chronotropic activities. To provide more related chemical entities for structure-activity relationship investigation, we used berberine as starting material and carried out its chemical modifications.
Oxidation of berberine under strong alkaline conditions [conc. KOH(aq)] provided 8-oxo-berberine. The introduction of Δ5 by treatment of 8-oxo-berberine with Pd-C or DDQ, however, was failed. Instead, selective 9-O-demethylation with yielded 13-hydroxy-8-oxo-berberine was observed for Pd-C treatment, and 13-hydroxylation occurred upon treatment with DDQ. This selective O-demethylation was also observed by treatment with conc.HCl(aq) under high temperature. Reduction of berberine with NaBH4 provided canadine (tetrahydroberberine), which upon treatment with iodosobenzene (PhI=O) under sonicating or heating conditions yielded berberal, together with minor 8-oxo-berberine and berberine. Berberal can also be prepared from berberine applying the same oxidation condition. Under such condition, 13-hydroxy-8-oxo-berberine and 8-oxo-berberine were obtained as by-products. We are currently searching for a better reaction condition to improve the yield of berberal. The anti-arrhythmic activity of these prepared compounds is currently in progress.
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