Canadine methochloride

It is of interest in this connection to note that the conversion of tetrahydroberberine into an anhydro-base of type E (p. 337) represents transformation from the berberine to the cryptopine type (p. 295), and that a-canadine methochloride occurs in Zanthoxylum brachyacanihum with its cryptopine analogue, y-homochelidonine ( -aiiocryptopine, p. 301). 

Optically active ochotensanes of structure (117) have been obtained from (+)-and (—)-/S-canadine methochloride (116 R = H) and iV-methylthalictricavine chloride (116 R = Me) by rearrangement with organometallic compounds, other products being the two Hofmann degradation products.122... 

This group is at present represented by four members -)-N-methyltetrahydroberberine chloride (a-l-canadine methochloride) (LXVIII), cyclanoline (LXIX) (55), steponine (LXX) (55), and phellodendrine. 

N-Methylcanadine chloride (canadine methochloride) was evaluated in the human immunodeficiency virus reverse transcriptase assay and found to be inactive (ICJ0 > 200 pg/ml)[229]. 

The bark of this West Indian tree yielded lupeol and d-sesamine in addition to five quaternary alkaloids, namely, chelerythrine, 1-canadine methochloride, candicine, and d-tambetarine, all isolated as chlorides as well as alkaloid-A (mp 266°-268°), which is not to be confused with alkaloid-A from Stephania rotunda (209). The plant has also been referred to as Z.follis oblongo-ovatis Browne, Z. clavaherculis SW., Z. caribaeum Hitchc., Fagara martinicense Lam. 

The naturally occurring quaternary tetrahydroprotoberberine types of alkaloids are predominantly in the a-form, except for the / -2-canadine methochloride. The stereochemistry of stylopine methohydroxide remains undefined (500). 

Treatment of (74S)-(-)-/8- and (14R)-(+)-/3-canadine methochlorides (58e) with organolithiums, lithium aluminum hydride, or sodium methyl-sulfinyl carbanion in tetrahydrofuran gave (+)-199 and (-)-2,3-methyl-... 

It should be noted that a-Z-canadine methochloride was isolated from Zantkoxylum brachyacanthum by Jowett and Pyman (176). 

Canadine is bitter and in small doses causes drowsiness and depression. In large doses it gives rise to transient excitement succeeded by depression and paralysis of the central nervous system. Its injection is followed by violent peristalsis with diarrhoea. It is said to have no effect on the blood pressure. The pharmacological action of canadine a- and p-methochlorides was examined by Laidlaw, who found both to have the curare-like action common to ammonium bases, the j8-isomeride being the more active the relative activities of tlie fom optically active forms are given as la da Zj8 = 1 9 12 28. 

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