Corydaline

Corydaline, C22H27O4N, was first isolated, obviously in impure form, from Corydalis tuberosa by Wackenroder (242). It has since been found in C. ambigua (24), C. aurea (28), C. Montana (29), and C. platycarpa (46). It crystallizes from hot methanol in stout hexagonal prisms and has 

4-300° (chloroform). In most plants it is associated with its oxidation product, dehydrocorydaline, and the alkaloid F57 (29) has recently been shown to be one of the forms of inactive corydaline (243). The dehydro base only was isolated from what was regarded as C. vernyi Franch. et Sav. by Makoshi (39), but it remained for Asahina and Motigase (38) to show that the plant source was C. decumbens. 

Corydaline has only been found in the d-form, which melts at 136°. It is readily soluble in choroform, moderately so in ether, and sparingly in 

Constitution. Many formulas have been suggested at various times for corydaline. The first, C1SH19O4N, due to Wicke (244) was modified by a number of authors until Freund and Joseph (52) arrived at the correct formula. 

In the course of work leading to the elucidation of the structure of corydaline at the time that these researches were undertaken the structures of none of the protoberberines were known, and most of this work is of historical interest only. Had the later work on berberine and tetrahydro-palmatine been available the determination of the structure of corydaline would have been an easy task. That it contains the same nuclear structure is indicated by its ready oxidation to dehydrocorydaline. Unlike the reduction of palmatine which gives a single product, the dl-tetrahydro base, the reduction of dehydrocorydaline gives rise to a mixture of meso-and racemic corydaline (245). The mesocorydaline has been resolved by means of d-camphorsulfonic acid, but the d-base is not identical with d-corydaline. It is obvious therefore that corydaline contains two asymmetric carbons. 

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Corydalis ambigua Cham, and Sch. Corybulbine, corydaline, dehydrocorydaline, protopine. Bases —(I). A quaternary chloride,... 

Special Reactions of Papaverine. Papaverine undergoes a number of reactions, which are of interest as providing methods of synthesis for other alkaloids, of which examples will be found under laudanosine, laudanine, laudanidine, codamine (pp. 187-195), berberine (p. 331), corydaline (p. 284), and glaucine (p. 311). 

Corydaline, C22H2,04N. (Items 8, 9, 31 list, pp. 170-2.) After the discovery of this alkaloid by Wackenroder, Wicke analysed well-crystallised salts and adopted the formula CigHig04N. Birsmann changed this to C22H23O4N, which Dobbie and Lauder altered to C22H29O4N, this in turn being modified by Freund and Josephi to C22H2,04N. 

Constitution. Corydaline eontains four methoxyl groups. Insight into the constitution of the alkaloid has been obtained principally by the study of its oxidation products, as indicated by the following tabular scheme. 

Dehydrocorydaline, C22H2304lSk (Items 8,14, 31 list, pp. 170-2.) This alkaloid is formed by the gentle oxidation of corydaline.It is a yellowish crystalline powder, m.p. 112-3° (dec.) the hydrochloride, B. HCl. 4H2O, forms yellow leaflets hydriodide, B. HI. 2H2O, small yellow needles aurichloride, B. HAUCI4, red-brown needles, m.p. 219°. Like berberine,... 

Dehydrocorydaline eontains four methoxyl groups. On reduetion it furnishes two stereoisomerides of eorydaline, m.p. 135°, and m.p. 158-9° (163-4° vac.), Spath) the latter ( 2f.9oeorydaline) by erj stallisation of the d-eamphorsulphonate can be partially separated into d- and Z-forms, the d-form of which is not identical with natural corydaline.The second isomeridc, m.p. 135°, has not been resolved into optically active components, but from the sulphonic acid the Z-compoiient has been isolated by crystallisation of the brucine salt, and this is taken to indicate that the inactive corydaline, m.p. 135°, is dZ-corydaliiie. °... 

Dehydrocorydaline exhibits many analogies with berberinc thus both are yellow and both are easily reduced, forming the colourless alkaloids, corydaline and tetrahydroanhydroberberine respectively. 

Papaverine was condensed with formaldehyde to methylenepapaverine (XXII), which on successive catalytic and electrolytic hydrogenation yielded two dZ-methyltetrahydropapaverines (XXIII), which on successive demethylation, condensation with formaldehyde and re-methylation yielded a mixture of bases, from which the two optically inactive corydalines (XXIV), jwesocorydaline, m.p. 163-4° (nac.), and dZ-corydaline, m.p. 132-3°, identical with the products obtained by the hydrogenation of dehydrocorydaline were isolated. For the conversion of corycavine to corydaline, see p. 304. 

Corytuberine, C43H21O4N. 5H2O. (Items 18, 31, 37 list, pp. 171-2.) This alkaloid, obtained by Bobbie and Lauder from commercial corydaline, crystallises in silky needles, m.p. 240° dec.), 282-65°... 

It should, however, be noted that though Spath and Kruta were unable to condense tetrahydropapaverines with formaldehyde to the berberine type of alkaloid, they found that tetrahydropapaverolines condensed with formaldehyde in both ways, and examples will be found under corydaline (p. 289) and the constitution of palmatine and the related bases (p. 343). 

Spath and Kruta have also prepared dZ-tetrahydropalmatine by the process described for meso- and r-corydalines (p. 289), and by condensing tetrahydropapaveroline with formaldehyde and methylating the product, obtained in poor yield, a mixture of tetrahydropalmatine and ftorcoralydine. 

Robinson (1934) has elaborated this into a scheme embracing hydrastine, berberine, epicryptopine, corydaline, sanguinarine and homochelidonine, though he points out that dihydroxyphenylalanine is labile and too easily convertible into indole derivatives to be capable of... 

C alkylation was used in the corydaline synthesis 194). LukeS and Dedek 195) obtained on methylation of l-methyl-2-ethylidenepyrrolidine a C-alkylation product, i.e., l-methyl-2-isopropyl-/l -pyrroline (106). Alkylation of the same enamine with ethyl bromoacetate was the first synthetic step in the preparation of D,L-pseudoheliotridane 196). 

These methods were applied to a synthesis of corydaline (469) (231), tetrahydrocorysamine (470) (235), and corybulbine (471) (236) (Scheme 95). Rather mild 13-methylation was developed by treatment of dihydroberberine (90) with 30% formaldehyde in 10% acetic acid (237,238). However, this method cannot be applied to an introduction of other C-13 substituents because aldehydes other than formaldehyde do no react. 

Corydalis yanhusuo W. T. Wang ex Z. Y. Su et C. Y. Wu China d-corydaline, corydalis, dl-tetrahydropalmatine, crybulbine, alpha-allocryptopine, tetrahydrocoptisine, corydalamine, tetrahydrocolumbamine, protopine, coptisine, dehydrocorydaline, columbamine, dehydrocorydalmine.33 Overdosage is toxic. Analgesic, sedative, hypnotic, synergistic, increase coronary flow. 

N.A. Corydalis, corydaline, leonticine, tetrahydropalmatine, protopine." Analgesic, antispasmodic, sedative. 

A-Acyliminium ions are versatile intermediates for synthesis of nitrogenous compounds, particularly alkaloids [154]. The conjugate system is very electrophilic such that it can be intercepted by various donors including carbonyl compounds and jt-systems. In comparison with a,p-unsaturated ketones the replacement of the a-carbon with a nitrogen atom accentuates the reactivity of these species. Ingenious applications of the JV-acyliminium ions include service to synthesis of corydaline [155], lycoramine [156], quebrachamine [157], and ajmaline [158], to name a very few. 

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