1-tetrahydropalmatine

Structure. Reduction of palmatine yields di-tetrahydropalmatine, and this can readily be reoxidized to palmatine. It differs from berberine in having four methoxyls, the methylenedioxy group of the latter being replaced by two methoxyls in the former. Since it yields corydaldine and hemipinic acid on oxidation with permanganate Feist and Sandstede (223) suggested structure XXIX, which should be rewritten to conform to the carbinol form analogous to XVII for berberine. Like berberine it forms 

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 d-form of this alkaloid was first isolated from Corydalis tuberosa by Spath, Mosettig, and Trothandl (58) but has since been isolated in the Z-, d- (m.p. 142°), and/or dl- (m.p. 151°) forms from the following plants Corydalis ambigua (dl-) (25, 26), C. aurea (1-, dl-) (5, 28), C. caseana (1-) 

Tetrahydropalmatine yields a hydrochloride which is moderately soluble in boiling water and only sparingly soluble in cold water. This property, together with the fact that the hydrochloride is readily extractable from hydrochloric acid solutions of plant extracts by means of chloroform, renders its isolation and purification a simple procedure. The hydrochloride of the dZ-form is appreciably less soluble than that of the d- or Z-forms and separates in stout prisms even from hot aqueous solutions. The alkaloid is readily oxidized by air and slowly becomes yellow owing to the formation of palmatine. This oxidation can be readily completed by means of alcoholic iodine solutions when palmatine iodide is formed, or it may be brought about by heating in dilute acetic acid with mercuric acetate (224). 

Structure and Synthesis. In addition to the proof of the structure of tetrahydropalmatine by virtue of its preparation from palmatine and the reverse oxidation, the resolution of the dZ-base was accomplished by means of d- and Z-tartaric acids in succession, the d-base d-tartrate and the Z-base Z-tartrate being the forms of least solubility (225). The d- and Z-bases had [a]n +291° (ethanol) and —294° (ethanol), respectively, the natural d-base having [a] +292.5° (58). Spath and Mosettig (226) have also related tetrahydropalmatine directly to tetrahydroberberine, that is to canadine. The d-, Z-, and dZ-forms of canadine were demethylenated by means of phloroglucinol and sulfuric acid yielding the base XXX in its three possible forms, the d-form having +307° (ethanol). These when 

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According to Huang-Minlon, Makoshi s base (I) is coptisine, while Chou s base, B, is dl-tetrahydropalmatine and D and E are I- and dl-tetrahydrocoptisine respectively. 

Manske has isolated from several papaveraceous plants an alkaloid aurotensine (items 9, 19, 23, 44, 47, 48 list, pp. 170-3) which occius in rhombic plates, m.p. 128° [a]n — 69-9° and appears to be an addition compound of I- and di-scoulerine (Manske ). Its dimethyl ether caseanine item 10 list, p. 170), m.p. 115-6° (hydrated) or 142° (ex benzene) must be tetrahydropalmatine (p. 292) and casealutine, found with caseanine, was shown later by Manske to be i-isocorypalmine. 

It may also be noted that Manske s base F 51 (item 22 list, p. 171) is isomeric with the two corypalmines and like them methylates to tetrahydropalmatine. 

Haworth, Koepfli and Perkin have shown that, like other alkaloids of the protoherherine series, tetrahydropalmatine is convertible by the general process (p. 302) into an alkaloid of the cryptopine type. The... 

Jatrorrhizine (Jateorhizine). (Items 6, 9, 11, 14, 18, 19, 21, 22 list, p. 329.) The iodide, C20H20O4NI. H2O, crystallises in reddish-yellow needles, m.p. 210-2° the chloride C20H20O4NCI. H2O, forms copper-coloured needles, m.p. 206°, and the nitrate golden-yellow needles, m.p. 225° (dec.). On 0-methylation, jatrorrhizine iodide yields palmatine iodide, and on reduction it is converted into dZ-tetrahydrojatrorrhizine, m.p. 217-8°, the d-form of which is corypalmine and which on 0-methylation yields tetrahydropalmatine (p. 292). ... 

Columbamine. (Items 1, 6, 9, 11, 18, 22 list, p. 328.) This base probably occurs among the phenolic alkaloids of ealumba root, but it has only been isolated in the form of dl-tetrahydrocolumbamine, Cj,H4gN(OH)(OMe)3, m.p. 223-4° (p. 291), which on methylation furnishes dZ-tetrahydropalmatine. 

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. 

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. 

Desmet P, Elferink P, Verpoorte R (1989) Left-turning tetrahydropalmatine in Chinese tablets. Ned Tijdschr Geneeskd 133 308... 

Li L et al. (2006) Liquid chromatography-tandem mass spectrometry for the identification of L-tetrahydropalmatine metabolites in Penicillium janthinellum and rats. Biomed Chromatogr 20(1) 95-100... 

Labeled muramine (395) was synthesized for biosynthetic studies from tetrahydropalmatine (27) in 35% overall yield via the von Braun reaction product 30c (Section II,A,2) and the alcohol 403 (Scheme 76) (42). Labeled 13-oxygenated muramines 405a and 405b were obtained by oxidation of dihydropalmatine metho salt (404) with osmium tetroxide (42). 

Vauquelin G, De Keyser J, Banyingela K, Vanhaelen M. ( )Tetrahydroanisocycline and ( )tetrahydropalmatine binding to D and D2 dopaminergic receptors in human putamen. Neurochem Int 1989 15 321-324. 

Chang CK, Lin MT. DL-Tetrahydropalmatine may act through inhibition of amygdaloid release of dopamine to inhibit an epileptic attack in rats. Neurosci Lett 2001 307 163-166. 

Corydalis decumbens (Thunb.) Pers. Xia Tian Wu (aerial part) Protopine, bulbocapnine, d-tetrahydropalmatine.33-240 Toxic if overdosage. Relieve pain after bone fractures, antihypertensive, antirheumatic. 

Stephania sinica DC Hua Qian Jin Teng (root) 1-tetrahydropalmatine, stepharotine, stepharine, tuduranine.33 Analgesic effect, treat stomachache, neuralgia, toothache. 

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. 

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