Ipecoside

There is a relatively large number of alkaloids which maybe considered as simple phenethyl amine [64-04-0] (59, R = H), CgH N, or tyramine [51-67-2] (59, R = OH), CgH NO, derivatives. These iaclude mescaline (61) from the small wooly peyotyl cactus l ophophora mlliamsii (L emaire) Coult. anhalamine (62) and lophocerine (63) from other Cactaceae, and the important antamebic alkaloids (—)-protoemetiae (64), (—)-ipecoside (65), and (—)-emetine (66) from the South American straggling bush Cephaelis ipecacuanha (Brotero) Rich. AH of these bases appear to be derived from tyrosiae (25,... 

IPA-water system, evolving separation strategies for, 22 322-325. See also Water-IPA-hexane system (-)-Ipecoside, 2 84, 85 Ipratropium bromide, 4 360t Iproclozide, 73 49... 

From dopamine, the pathway of tetrahydroisoquinoline alkaloids, such as emetine and cephaeline (Figure 37), also begins. Dopamine and secologanin undergo a Mannich-like to produce A-deacetylisoipecoside and ipecoside, and after hydrolysis and transformation, this is converted to emetine and cephaeline. 

These alkaloids have a phenyl or phenylpropyl nucleus. The group includes simple phenyl amine (tyramine, hordenine), catecholamine (dopamine, noradrenaline, adrenaline), simple tetrahydroisoquinoline (mescaline, anhalamine, anhalonine, anhalonidine), benzylisoquinoline (e.g., papaverine), phthalideiso-quinoline (e.g., noscapine), phenethylisoquinoline (autumnaline, floramultine and kreysigine), tetrahydroisoquinoline (emehne and cephaeline) and terpenoid tetrahydroisoquinoline (secologanin and ipecoside) alkaloids. 

Finally, X-ray crystallographic analysis of 0,0-dimethylipecoside (143), together with the knowledge that hydrolysis of ipecoside (19) produces D-glucose, has established its structure and absolute stereochemistry (7/5). The position of the double bond in the ( )-unsaturated lactam acid 144, a synthetic intermediate for the emetine precursor ( )-45, has been inferred from chemical and spectroscopic evidence (285) and confirmed by an X-ray study (286). 

The close biogenetic relationship of the ipecac and monoterpenoid indole alkaloids has already been reviewed in several places (3,5,117,287). In the case of the ipecac alkaloids, tracer experiments (288) have shown that labeled geraniol (146) and loganin (148) are incorporated by Cephaelis ipecacuanha into radioactive cephaeline (149) and ipecoside (150). Thus, the C9-C,0 units of the ipecac alkaloid and ipecoside, represented by thickened lines in formulas 149 and 150, are of monoterpenoid origin from geraniol (145), and loganin (147) acts as a precursor for both alkaloids. The incorporation of glycine into the C9 unit of cephaeline (2) in Cephaelis plants has also been reported (289). 

In the meantime, the formation of the main alkaloids in C. ipecacuanha under a variety of conditions has been extensively investigated emetine (1) in callus cultures (49) and under the effects of L-tyrosine supplementation (5t)) emetine (1) and cephaeline (2) in Panamanian ipecac (57), in Nicaraguan ipecac (52), in regenerates obtained by clonal propagation (53,54), in tissue cultures (55) and under the effects of exogenous feeding of shikimic acid and L-phenylalanine (55), in cell suspension and excised root cultures (57), in adventitious root cultures (58), and in callus cultures (56,59) and the effects of age and electrokinetic potential (60) ipecoside (7) in the roots (61) and the effect oi Azotobacter, leaf mold, and farmyard manure on alkaloid content (62). In addition, micropropagation systems for C. ipecacuanha have been developed (63-65). 

G. Ipecoside, Alangiside, and Related Tetrahydroisoquinoline-Monoterpene Alkaloid Glucosides... 

When the last review on the ipecac alkaloids and /3-carboline congeners (1) was prepared, the chemistries of (-)-ipecoside (7) and (-)-alangiside... 

From the dried roots of C. ipecacuanha, Nagakura and co-workers (17,18) isolated six new tetrahydroisoquinoline-monoterpene glucosides, that is, 6-O-methylipecoside (8), ipecosidic acid (10), neoipecoside (15), 7-0-methylneoipecoside (16), 3,4-dehydroneoipecoside (17) (conceivably an artifact formed from 15 in the extraction process), and demethylalangiside... 

The role of secologanin was studied15 by feeding [0-met/iy/-3H,6,6-3H2]secolo-ganin to C. ipecacuanha plants activity was incorporated into all three alkaloids and in the case of ipecoside the distribution of activity was shown by degradation to correspond to an intact incorporation. 

The specific incorporation of (26) rather than its epimer (25) into cephaeline (28) and emetine (29) is surprising when one compares the configuration at C(5) of (25) with that at the corresponding position [C( 11 b)] of (28) and (29). The absolute configuration of (25) is rigorously established by relation to ipecoside.16... 

In view of the importance of the isoquinoline system in biosynthesis it is surprising that so little effort has been devoted in the past to the biosynthesis of the basic ring system. No doubt the success of this investigation in the peyote cactus will stimulate further work in other systems. It is likely that the normal pattern will involve condensation of a phenethylamine with the appropriate pyruvic acid. However, reference has already been made to ipecoside (27) (Scheme 3) in which the isoquinoline system is formed by condensation of the phenethylamine with an aldehyde [secologanin]. Presumably the corresponding aldehyde, rather than a pyruvic acid, will be found to serve as precursor for the phenethylisoquinolines,3 5 and also for the isoquinoline alkaloids of the Lophophora cactus such as lopho-cerine (66). 

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