Of corypalline

Corypalline, CnHijOjN (Corydalis spp. Nos. 9, 22 list, p. 170). This phenolic base, m.p. 168°, picrate, m.p. 178°, contains one methoxyl group and on methylation yields 2-methyl-6 7-dimethoxytetrahydrof5oquinoline, Ci2Hi,02N, m.p. 82°, and on ethylation, 2-methyl-6-methoxy-7-ethoxy-tetrahydrofsoquinoline, m.p. 65°, whence the free hydroxyl appears to be at C and this has been confirmed by the synthesis of corypalline by a method analogous with that used by Spath, Orekhov and Kuffner. Corypalline is therefore hydrohydrastinine (XII) with the methylenedioxy group replaced by MeO at C and. OH at C (Manske). ... 

One of the most reliable electrochemical methods for the synthesis of alkaloidal skeletons is the oxidative coupling of phenolic and related compounds. A typical early example is the oxidative coupling of corypalline 1 to its dimer 2 ... 

The hydrastinine derivative (4) has been converted into the diol (5), which has been synthesized from the glycidic ester (6) via the diester (7)8,9 (Scheme 1). The dissociation constants of corypalline and isocorypalline in acetonitrile have been measured.10... 

Treatment of corypalline (13) with lead tetraacetate leads57 to the quinol acetate (14) which rearranges in acetic anhydride-sulfuric acid to yield the 4-acetoxytetrahydroisoquinoline (15). The reduction of the lactol (16) to 4-hydroxytetrahydroisoquinoline (17) has been reported.70... 

Stock and Shia studied the dissociation constants of corypalline (lc) and isocorypalline in acetonitrile (386). 

On methylation it yields 2-methyl-6,7-dimethoxytetrahydroisoquinoline (m.p. 82°), and upon ethylation, 2-methyl-6-methoxy-7-ethoxytetrahydro-isoquinoline (m.p. 65°). The synthesis of corypalline was accomplished by a route parallel to that used by Spath, Orekhov, and Kuffner (39) in their synthesis of salsoline. 

Quinol acetates can also be used in halogenation, as in the C-8 bromina-tion of corypalline through treatment with lead tetraacetate followed by 48% HBr. Tetrahydrobenzylisoquinolines possessing a phenol at C-7 can also be chlorinated by a similar procedure using concentrated HCl in lieu of HBr. ... 

The experiments by Canonica et al. (1981) suggest a third plausible formation of simple isoquinoHnes with no carbon-1 substituent in plants mainly producing alkaloids of the benzylisoquinoline type. Treatment of the benzylisoquinoline N-methylcoclaurine with ascorbic acid oxidase, an enzyme widespread in plants, resulted in benzyhc fission giving about 40% yield of corypalline, its quaternary 1,2-dehydroderivative and benzyl alcohol. Thus, both isoquinolones and simple isoquinolines may be formed directly by the action of oxidative enzymes in benzyl-isoquinoline-producing plants. 

Corypalline (165 R = H)249 could be oxidatively dimerized electrochemi-cally in overall yields ranging from 44 to 85% depending on experimental conditions. Two types of dimers are obtained, the amount of carbon-carbon dimer 166 decreasing when R was varied from H through methyl to ethyl, and the product distribution shifted toward the carbon-oxygen-carbon dimer 167, presumably because of steric hindrance250 [Eq. (103)]. 

Since many isoquinoline alkaloids incorporate a guiacol moiety, we first tried to oxidize the most accessible 6-methoxy- and 7-methoxy-l,2,3,4-tetrahydroisoquinolinols (types A and B) with LTA. Later, tetrahydro-isoquinolinols of type C were also used. In spite of Wessely s statement (16) that LTA oxidation of both vanillin and isovanillin affords the corresponding o-quinol acetates, for a while we were able to obtain not the o-quinol acetate 2 from corypalline (1) but the p-quinol acetate 3 (17). At the outset of our study (IS), LTA oxidation of isocorypalline (4) gave no isolable o-quinol acetate 5, 4-acetoxyisocorypalline (6) being isolated instead. 

Lemaireocereine has been isolated from Backebegia militaris and a new quaternary alkaloid, pycnarrhine, identified as 7-hydroxy-6-methoxy-2-methyl-3,4-dihydroisoquinolinium chloride, has been isolated from Pycnarrhena longifoliaCorypalline (1 R = H) has been oxidised by lead tetra-acetate to the dienone (2), which reacts with veratrole and with corypalline in the presence of trifluoro-... 

O-demethylation and reetherification or methylenation of the liberated phenolic groups (346-348). The alkaloid corypalline (lc) can be conveniently prepared from 6,7-dimethoxy-3,4-dihydroisoquinoline (349). The first step is partial demethylation of the methoxyl at C-7. It gives rise to the monomethoxy derivative which on hydrogenation affords corypalline (Scheme 1). 

Scheme 1. Transformation of 6,7-dimethoxy-3,4-dihydroisoquinoline into corypalline (1 iff (349).

Corypalline was found by Manske (40) in Corydalis pallida and in the seeds of C. aurea. The base melts at 168° picrate, m.p. 178°. 

Some simple isoquinoline alkaloids (carnegine, salsoline, corypalline, hydrohydrastinine) may be considered as bio-products of the interaction of hydroxytyramine and acetaldehyde or formaldehyde, followed by methylation. Actually, Schopf and Bayerle (93) obtained a surprisingly high yield of norcarnegine by carrying out this condensation under mild ( physiological ) conditions, that is, at pH 5 and 25°. 

A new base, uberine, of structure (1), has been isolated from Dolichothele uberiformis O-Methyl-corypalline (2 R = Me) has been detected by mass spectrometry in Pilosocereus guerreronis, and corypalline (2 R = H) has been synthesized by Pictet-Spengler cyclization of N-methyI-/5-4-benzyloxy-3-methoxyphenyl-ethylamine, followed by debenzylation. A number of N-substi-tuted salsolidine derivatives (3), where R is PhCH2, PhS02, Me2CH, P-O2NC6H4,... 

Corypalline has been dimerized electrochemically in overall yields of 44-857o, depending upon experimental conditions. In general, the product was mainly carbon-carbon dimer with a small amount of the carbon-oxygen dimer. 

Tani C, Nagakura N, Kuriyama C (1978) Studies on the alkaloids of papaveraceous plants XXXI. Separation of the alkaloids by droplet countercurrent chromatography. The alkaloids of Corydalis ophiocarpa Hook, et Thoms. Yakugaku Zasshi 98 1243-1251 Theuns HG, Vlietstra EJ, Salemink CA (1983) Corypalline and O-methylcorypalline, two alkaloids horn Papaver bracteatum. Phytochemistry 22 247-250 Urzua A, Cassels BK (1978) Alkaloid chemosystematics, chemotaxonomy and biogenesis in the Atherospermataceae. Lloydia 41 98-113... 

---