Berbine

The nomenclature and numbering of formulas for berberine and its derivatives is based on the system adopted by Buck, Perkin and Stevens for the parent substance of the series, protoberberine (XXIV). Awe has suggested that tetrahydroproioberberine should be called berbine and used as the basis of a system of names for these alkaloids. 

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... 

All the 7,8-secoberbines incorporate an JV-methyltetrahydroisoquinoline moiety with two or three oxygenated substituents at C-l, C-2, and C-3. The lower aromatic ring possesses four substituents in a vicinal arrangement of which two are alkoxyls and the third the berbine bridge carbon. The latter may occur in different oxidation states as an aldehyde (in 1 and 2), an alcohol (3-6, 8, 9), or a carboxylic acid (7). 

H-NMR chemical shifts of the heterocyclic rings of selected substances are listed in Table 5 (bicyclic compounds). Table 6 (azepino[2,l-fl]isoqui-nolines). Table 7 (several pyridobenzazepines), and Table 8 (several homo-berbine-type isoquinobenzazepines). 

The protoberberinium alkaloids are derivatives of the 5,6-dihydrodibenzo[n,g]quin-olizinium ion (95). There exist also alkaloids which are deriyatives of berbine (5,6,13,13a-tetrahydro-8i7-dibenzo[a,g]quinolizine, 94). Ban et al. have shown that dehydrogenation of berbine with mercury(II) acetate will afford the parent protoberberinium salt (95) in 75% yield (60CPB183). 

Dibenzo[a,g]quinolizinium ion is the prototype of a series of compounds initially prepared as intermediates for the synthesis of berbine alkaloids but which, as a class, have recently attracted medicinal interest per se (Scheme 99, Table 11). 

Intramolecular Iminium Ion-Sulfide Charge-Transfer Association A Recurring Theme in the Study of Thiaspirane Alkaloids R. T. LaLonde, Acc. Chem. Res., 1980,13, 39-44. Recent Advances in the Chemistry of Berbine Alkaloids G. D. Pandey and K. P. Tiwari, Heterocycles, 1980,14, 59-82. 

Pd(OAc)2] in the presence of PPh3 was used as catalyst. The use of vinyl bromides in lactam formation has also been reported.498 Imides were obtained from aryl bromides. The method has further been applied to the synthesis of diazepam and 1,4-benzodiazepines499 and to a-methylene lactams and lactones.S00 501 In connection with the synthesis of natural products, the reaction has been employed in the preparation of hexadehydrohimbane,502 anthramycin503 and berbine derivatives.504 The catalyst was prepared in situ from [Pd(OAc)2] (106) and PPh3 in all cases. The mechanism of lactam formation is analogous to that for amides (Scheme 42). 

LaKind, J.S., Berbin, C.M., Narman, D.Q., 2001. Infant exposure to chemicals in breast milk in the United States What we need to learn from a breast milk monitoring program. Environ. Health Perspect. 109, 75-88. 

This substitution method has been extended to an annelation reaction which is applicable to the synthesis of berbine (berberine) type alkaloids 55. 

Treatment of a quaternary salt (14) with concentrated alkali causes disproportionation to occur to yield an isocarbostyril (13) and a 1,2-dihydroisoquinoline (6).25 The reaction, which probably proceeds via the pseudobase (15), has been used26 in a modified berbine ring... 

A total of 10 berbines (27-36) have been reported as constituents of four different species of Guatteria. (—)- 10-O-Demethyldiscretine (31) is the only sub-... 

With the foregoing caveat in mind, and considering the alkaloids found in higher concentrations, Guatteria seems to be on the whole a rather typical an-nonaceous genus characterized by the almost universal presence of aporphinoids. These compounds are often accompanied by unexceptional berbines and/or pro-toberberines as well as occasional monomeric benzylisoquinolines. 

The phenanthridine skeleton is synthesized by photocyclization of the enamides prepared from cyclohexanonimines and benzoyl chlorides (17,18). The benzo[c]phenanthridine skeletons are formed from the enamides prepared from 2-tetralonimines and benzoyl chlorides (19,20). More conveniently, the skeletons of protoberberine alkaloids are readily synthesized from the enamides prepared by simple acylation of 1 -methyl-3,4-dihy-droisoquinolines with benzoyl chlorides (21-24). This berbine synthesis is one of the most typical examples of the application of enamide photocyclization to alkaloid synthesis and can be further extended to the facile synthesis of the skeletons of the yohimbine group of indole alkaloids (25,26). 

As a further extension of photocyclization of the enamides prepared from 1-methylisoquinolines, Naito and Ninomiya (67) and Lenz (48) synthesized aza analogs of berbine, azaberbines, by irradiation of pyridine analogs of the parent enamides (27) (Scheme 57). 

These thermal cyclizations offer a promising route for the synthesis of berbine compounds with electron-withdrawing groups in ring D (Scheme 59). 

Successful berbine synthesis summarized in Section IV,C prompted Nin-omiya s group (25,26,117,118) to extend enamide photocyclization to har-malane, therefore giving rise to a novel and facile synthesis of polycyclic heterocycles such as the yohimbine group of compounds. Before reductive photocyclization was introduced, the use of nonoxidative photocyclization with indole alkaloids was limited to simple systems and those possessing a large degree of aromaticity. 

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