Coreximine

Occurrence. Coreximine, C19H21O4N, has been isolated only from Dicentra eximia (0.007%) (28). It crystallizes with great facility when a concentrated solution of it in chloroform is diluted with methanol. The colorless stout prisms thus obtained melt at 262° to an orange-colored liquid. 

Structure. Coreximine has two methoxyls and two phenolic hydroyls, and when methylated with diazomethane it yields a tetramethoxy compound, melting at 177°. Ethylation similarly yields a dimethoxydiethoxy base melting at 131° (28). The tetramethoxy compound is isomeric but not identical with tetrahydropalmatine, and like the latter it is readily oxidized in air to a yellow base, and when racemized by oxidation with mercuric acetate followed by reduction with zinc and hydrochloric acid it gave rise to a base (m.p. 157°) identical with norcoralydine (LXIX) (227). Coreximine is therefore a bisdesmethyl derivative of LXIX (271). Four such compounds are possible if vicinal hydroxy compounds are excluded. 

When th 0,0-diethyl ether of coreximine was oxidized under conditions which favor the formation of corydaldines there was obtained l-keto-6-methoxy-7-ethoxytetrahydroisoquinoline (XLII), and this serves to locate one hydroxyl at position 2 (LXX). The location of the second hydroxyl could not be carried out by further oxidation of the diethyl ether because only 4-methoxy-5-ethoxyphthalic acid could be formed. It was then assumed that the natural synthesis of coreximine involved ring closure of a benzylisoquinoline and that this could only occur if the condensation posi- 

Pavesi, (from) AUi reale ist. botan. univ. Pavia, 9 (1906) Chem. cenlr, 

Richert, Rev. centra estud. agronomia y veterinaria univ. Buenos Aires, 11 

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On treatment of N-methylpapaverine, formed by the lithium aluminum hydride reduction of papaverine methiodide with phosphoric acid, N-methylpavine is formed which is identical with the racemic alkaloid argemonine. This reaction was used for the synthesis of the alkaloid (-h)-coreximine (268) (174) and similar compounds containing the proto-berberine grouping in the molecule (269,270). 

Corydalis incisa (Thunb.) Pers. C. bungeana Turcz. Chuan Duan Chang Cao Di Ding Zi Jing (Corydalis) (whole plant) Protopine, pallidine, sinocecatine, corynoline, isocorynoline, coptisine, corycavine, acetylcorynoline, corynoloxin, coreximine, reliculine, corydamine, scoulerine.33,50 For rectal prolapse, abscesses, hemorrhoids. 

A patent describes the production of coreximine and its analogues from benzo-cyclobutenes of type (65) by the action of heat followed by reduction,88 and in a... 

New bases that have been isolated are represented by norpallidine (124 R = H), from Fumaria vaillantii, identified by its Eschweiler methylation to pallidine (124 R = Me).147 Pallidine has been shown to be produced (together with coreximine,... 

Reticuline has been biotransformed into the morphinandienone pallidine, the aporphine isoboldine, and the protoberberines coreximine and scoulerine by rat liver enzyme 37 and the use of isolated enzymes in the formation of natural products, including aporphines, has been reviewed.38... 

A second general method for the synthesis of the protoberberine alkaloids has been described by Battersby et al. (116). The method, which utilizes a 1,2-dihydroquinoline as a key intermediate, has been used to synthesize ( + )-norcoralydine (XXXIX R = CH3) and (+ )-coreximine (LXXIX), as illustrated for the latter in Chart III. 

In addition to the new synthetie approaches described, some successful syntheses have been accomplished by using previously described routes. Among these are the syntheses of ( )-coreximine (LXXIX) (mp 237°-238°) and its A-methyl derivative, ( )-phellodendrine (LXXVII) (mp > 300°), completed by Tomita and Kunitomo (115). The route... 

Using the same approach these authors (120) have synthesized the coreximine isomers, LXXXVIII (mp 232°-233°), LXXXIX (mp 211°-213°), and XC (mp 253° dec.) together with their respective iV -methyl derivatives XCI (iodide, mp 264°-271°), XCII (iodide, mp 282° dec.), and XCIII (iodide, mp 264°-270°). 

In the biosynthesis of benzylisoquinoline alkaloids, a plausible N-oxide intermediate is suggested. Thus, reticuline Ai-oxide (768) was treated with CuCl in MeOH in the absence of dioxygen and then with NaHS03 to afford corytuberine (769) (61%), while the use of excess FeS04 provided coreximine (770) and scoulerine (771) in 42 and 23% yields, respectively (Scheme 152). ... 

Core valence bifurcation index 75, 76 Coreximine, formation of 1306 Cotitration studies 335 Coulometric arrays 960, 961 Coumarans—see also Phenylcoumarans formation of 753-758 Coumaric acid 1057 Coumarins—see 4-Methylcoumarin Coumestans, synthesis of 1219, 1222 Coupled clusters 3... 

Coreximine was shown to be elaborated by this much investigated plant and it was shown to be derived from labeled ( )-reticuline... 

Kametani and Ihara (237, 237c) observed that treatment of optically active protoberberine alkaloids, namely (— )-coreximine, ( —)-tetra-hydropalmatine, and (— )-norcoralydine with hydrogen in the presence of platinum oxide afforded the corresponding racemic tetrahydro-protoberberines. Kametani et al. (237b) found on the basis of X-ray analysis and NMR and mass spectral data that the skeleton of capauri-mine and capaurine would be cis-quinolizidine. 

The isolation of the alkaloids of the protoberberine type (102) and the synthesis of columbamine from berberine (101) have been reported. The synthesis of coreximine, scoulerine, and tetrahydropalmatine have been described (59, 235, 236). The synthesis of alkaloids having a protoberberine skeleton has been reviewed (374). 

Details of the synthesis of berberastine via a 3-aryltetrahydroisoquinoline have appeared. In a new modification of this route, separable mixtures of scoulerine (123 R = OH R = H) and coreximine (123 R = H R = OH), stereospecifically labelled with tritium at C-13, have been synthesized from stereospecifically labelled a-tritiobenzyl alcohols (Scheme 11). ... 

Numerous reports have also been published on the separation of the individual alkaloids by using ion exchangers (301, 302), various solvents of different pH (303), or multibuffered extraction systems (102, 103, 304-306). The isolation of minor bases from extracts of P. somniferum (254,282, 307-311) and of Fumaria officinalis (166) has been reported. The separation of the bases obtained from this plant material was also carried out by countercurrent distribution (312) and column chromatography (313, 314). The alkaloid coreximine was detected in P. somniferum by an isotope dilution method which was based on the biosynthesis of this alkaloid from reticuline (249). The isoquinoline type of quaternary alkaloids can be... 

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