Berberine, tetrahydro

Die Konfiguration des natiirlichen (+)-Laudanosins, sowie verwandter Tetrahy-dro-isochinolin-, Aporphin- und Tetrahydro-berberin-alkaloide, by H. Corrodi and E. Hardegger, Helv. Chim. Acta, 39 (1956) 889-897. 

The synthesis of allocryptopine by Haworth and Perkin (82) was the first application of the process already outlined for cryptopine and protopine. This choice was made because the starting material, tetrahydro-berberine ((XXIX) with the methylenedioxy and the methoxy groups interchanged) was readily available. Furthermore, Pyman (18) had already made a full investigation of the decomposition of the methohydroxide to... 

Patents for the preparation and use of quaternary salts of tetrahydro-berberines " and of esters of protoberberines of general structure (98), where R ... 

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). 

Berberine, 162, 169, 170, 171, 287, 328, 329, 331, 344, 345, 631 Berberine, quaternary ammonium bases from tetrahydro-derivative, 337 Berberine and related bases, pharmacological action, 345 syntheses, 334 Berberineacetone, 333 cptBerberine, 297 profoBerberine, 336 4-Berberines, 335 Berberinium hydroxide, 333 Berberinol, 333 Berberis spp., 328, 331, 346 Berberoline, 332 Berberonic acid, 507 Berberrubine, 329, 343 Berbine, 336 Betaine, 518 Bicucine, 170, 209... 

Protoberberine Alkaloids.—In the course of the bioconversion of the proto-berberine scoulerine (65) into chelidonine (62) and phthalide-isoquinolines, e.g. narcotine (63), C-13 becomes oxidized.61 Ophiocarpine (68), with a hydroxy-group at C-13, represents an intermediate stage in the modification of the protoberberine skeleton, and results62 of tracer experiments have shown that scoulerine (65) is also to be included in the biosynthesis of this alkaloid. Tetrahydro-protoberberine (67) is also a precursor, its incorporation indicating that C-13 hydroxylation is a terminal step. As for other protoberberine derivatives,63 nandinine (64) was not assimilated,62 and it follows then that (65) is probably converted into (67) by way of isocorypalmine (66). 

Berberines are reported to be reduced to dihydroberberines rather than the tetrahydro-compounds by sodium bis(2-methoxyethoxy)aluminium hydride.80 Partial reduction of coralynium salts affords the tertiary dienamine (55), autoxida-tion of which, at pH 8, yields the betaine (56) this can be oxidized by peracids to 6 -acetylpapaveraldine (57), obtainable directly from the dienamine (55) by photolysis in the presence of air. The diketone reacts with hydrazine to give the 1,2-diazine (58).81... 

The chiroptical properties of the tetrahydroberberine alkaloids in relation to their absolute configurations have been studied.139 The pharmacokinetics140 and intercalative binding141 of berberine, the antipsychotic properties of tetrahydro-... 

The system of nomenclature for alkaloids of the tetrahydro series is somewhat confusing. Naturally occurring members of this series often occur in one of their optically active forms understandably, at the time of isolation, they were given trivial names of their own. The trivial names have survived despite the fact that the relationship of these alkaloids as tetrahydro derivatives of known quaternary alkaloids of the dibenzo Iquinolizine series (cf. berberine), which themselves have trivial names, has in most cases been clearly established. Although it would seem desirable to retain the names of the quaternary alkaloids of the series as parent names and to designate alkaloids of the tetrahydro series accordingly, this has its disadvantages in that the related quaternary bases of some alkaloids of the tetrahydro series are not known to occur in nature. 

Im Gegensatz dazu wird beim gelben Berberin mit Zink/Essigsaure die C=C- und C=N-Doppelbindung reduziert, und man erhalt 3,4-Dimethoxy-10,l 1 -methylendioxy-7,8,12b, 13-tetrahydro-5H-(isochinolino- [3,2-a]- chinolin 4 ... 

Various Reactions in the Side-Chains of Thiophens. - The preparation of various iV-substituted thieno[3,2-/]morphans from 2,5-dimethylthieno[3,2-/Jmorphan has been described. Several thiophen isosteres of proto-berberine alkaloids have been prepared, starting from amides between 3-thienylacetic acid and substituted )3-phenylethylamine or 3-(3-thienyl)ethyl-amine, followed by classical cyclization to dihydroisoquinolines, reduction to the tetrahydro system, and Mannich-type reaction with formaldehyde. 

Since canadine is easily oxidized by atmospheric oxygen to berberine there is httle doubt that berberine is a constituent of all plants which contain canadine. However, there are many occurrences of berberine unaccompanied by canadine, particularly in plants of the Berberidaceae and Menispermaceae, and it would seem that there is present in these plants a specific oxidative system which converts the presumably intermediate tetrahydro bases into the quaternary compounds. 

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. 

Structure and Synthesis. When Buck and Perkin (228) attempted to apply the Pictet and Gams synthesis (220) of berberine to epiberberine they obtained an isomer, tetrahydro- -epiberberine (XXXIII). Subsequently, Haworth and Perkin achieved a total synthesis which is detailed in connection with the synthesis of cryptopine. Oxidation of sinactine with iodine in boiling alcohol yields epiberberinium iodide, from which the chloride was prepared by treatment with silver chloride, and this was identical with epiberberinium chloride prepared from cryptopine (235). Finaly, Spath and Mosettig (236) resolved the dZ-tetrahydroepiberberine (m.p. 170°) (XLIII) from cryptopine by means of d- and Z-tartaric acids in succession and showed that the Z-form, [a] —302° (chloroform), was identical with the natural alkaloid. The cZ-form had the same numerical value for its optical rotation and melted at 178-179°. 

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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