Palmatine, tetrahydro

Berberine is probably the most widely distributed alkaloid. It and the allied alkaloids palmatine, jatrorrhizine, columbamine and coptisine occur somewhat frequently in the Rhcnadales (list, p. 169) as the tetrahydro-derivatives, but, in the botanical families referred to in the distribution list below, the tetrahydro-derivatives are exceptional and the unreduced alkaloids usual. The associated alkaloids include two members of the aporphine group, domesticine and t odomesticine (p. 315), one member of the cryptopine group, y-homochelidonine (p. 294) and two members of the double woquinoline type, viz., berbamine and oxyacanthine (p. 346). 

Palmatine and Associated Alkaloids. Palmatine, jatrorrhizine (jateorhizine) and columbamine were first isolated from ealumba root (Jateorhiza palmata Lam., Miers) as a result of the work of Giinzel followed by that of Feist, but all three have sinee been found in other genera. All three are quaternary bases, soluble in water, and methods for their isolation have been deseribed by Giinzel, Feist, and Spath and Polgar, usually dependent upon their preeipitation as iodides, or their reduetion to the tertiary tetrahydro-bases. The latter oeeur naturally in the Rhceadales and have been deseribed already (p. 284). A method for the separate estimation of the alkaloids of ealumba root has been described by Neugebauer and Brunner. " ... 

Constitution. Comparison of the empirical formula of the three alkaloids, and the fact that jatrorrhizine and columbamine each stands to palmatine in the relation of a monohydric phenol to its methyl ether, makes it clear that the only difference between jatrorrhizine and columbamine must be in the position of the free hydroxyl group. The method by which this point was settled is described in dealing with the two tetrahydro-derivatives of these alkaloids (p. 291). The constitution of palmatine (XXV R = R = Me) is dealt with under tetrahydropalmatine, but it is still necessary to describe the complete synthesis of this alkaloid via oxypalmatine (XXVII) and tetrahydropalmatine. 

The chemical shift of C-8 may be used to determine the position of the oxygenated substituents in ring D. A comparison of the spectra of tetrahydro-palmatine (69) and xylopinine (70) (49) showed that C-8 in (70) is deshielded... 

Optical rotatory dispersion (ORD) spectra have also been used to assign absolute configiu-ation to these alkaloids. (— )-Tetrahydro-palmatine (XLI) exhibits a negative Cotton effect in the region of 300 mp. and this has been correlated with the representation of its absolute configuration as 14 R on the basis of a comparison with the positive plain dispersion curve shown in this region by (+ )-l,2-diphenylethylamine (XLIX) (97). 

Slavikova and Slavik 181) have isolated a diphenolic protoberberine alkaloid, HFl, C19H21O4N (mp 20I°-203° [a]j, — 356° in CHCI3) from Hunnemannia fumariaefolia Sweet. It was characterized as a (— )-0,0-bisdemethyltetrahydropalmatine by methylation to (— )-tetrahydro-palmatine. The position of the phenolic hydroxyl groups had not been determined, but mass spectrometry indicates one is in ring A and the second in ring D. 

The cyclisation of appropriately substituted iV-benzyi quaternary salts of 3,4-dihydroisoquinolines has afforded tetrahy-droberberines. For example the electrolytic reduction of the salt (219, R=CH2Br) and the treatment of -the salt (219, R=CH2 SiMe2) with sodium fluoride yields xylopinine (220, R =H, R = OMe) (T. Shono et al.. Tetrahedron Letters, 1978, 4819 S. Takano, H. Numata and K. Ogasawa, Heterocycles, 1983, 2, 417). The condensation of 6,7-dimethoxy-3,4-dihydroisoquinoline with methyl 2,3-dimethoxy-6-bromomethylbenzoate in acetonitrile in the presence of zinc as a reducing agent affords tetrahydro-palmatine (220, R =0Me, R =H) (H. Hamaguchi et al. J.org. Chem., 1983, 1621) and the condensation of the same dihy-... 

The tubers of this plant yielded six quaternary alkaloids (190), four of which were shown to be palmatine, jatrorrhizine, columbamine, and the ubiquitous magnoflorine. One of the remaining ones (A) was shown to be dehydrocorydalmine and the other (B), shown to be new, was named stepharanine (hydrochloride, mp 274°), and was shown to be CVII. This was accomplished by partially methylating the alkaloid to a mixture of palmatine, columbamine, and dehydrocorydalmine (191). Tetrahydro-palmatine and stepharine were also reported to be present. 

C. poAlida (Thunb.) Pere. Corypalline (44) Capauridine (45) Capaurimine (45) Capaurine (45) Scoulerine (45) d-Tetrahydropalmatine (45) di-Tetrabydropalmatine (45) FSl, CttHwOgN, m.p. 171" (45), yields dl-tetrahydro-palmatine on methyls-tion Protopine (45)... 

An alkaloid, shobakunine, isolated from Mahonia philippinensis (134) and Archangelisia flava (152), was shown to be a mixture, possibly molecular, of berberine and palmatine, and its reduction product, tetrahydro-shobakunine, was either a compound or mixture of dZ-canadine and of dl-tetrahydropalmatine. 

The mixture of the iodides are separable from the palmatine iodide by virtue of their phenolic nature and, therefore, their solubility in aqueous alkali. Jatrorrhizine generally being the major constituent it has been obtained in a satisfactory state of purity by direct crystallization of the iodide, but columbamine has only been isolated in pure form as its tetrahydro derivative. The structures of these alkaloids are discussed under cory-palmine, which is tetrahydrojatrorrhizine, and isocorypalmine, which is tetrahydrocolumbamine. 

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. 

Cell culture Substrate Canadine Sty1opine (pkat/g dry weight) Sinactine Tetrahydro- palmatine Nandinine... 

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