Berberine isolation

Palmitine and berberine isolation artifacts. Marek and co-workers have reported a study of the structures of common isolation artifacts of the widely distributed alkaloids palmitine and berberine (99) that are frequently formed from adduction of simple solvent molecules during isolation. The authors reported chemical shift assignments for the reported molecules that were established from HMBC data (Table 5). 

Freile ML, Giannini F, Pucci G, Sturniolo A, Rodero L, Pucci O, Balzareti V, Enriz RD (2003) Antimicrobial activity of aqueous extracts and of berberine isolated from Berberis heterophylla. Fitoterapia 74(7-8) 702-705... 

Although some alkaloids of this type show pharmacological activity, very few of them have been used then ieutically. Berberine, isolated from Berberis vulgaris, has antimicrobial and protozoodde activity. The biogenesis of scoulerine, a tetrahydroprotoberbmine alkaloid, is shown in Scheme 11. This type of alkaloid has been reviewed (48-50). 

The reaction of oxyberberine (58) and berberine (15) with dichlorocarbene has been previously reviewed (11). An interesting product was the keto lactam 189, which was obtained from 58 via the adduct 188 (Scheme 34) (105). This product was later isolated from Berberis darwinii and named magallanesine (106) however, this alkaloid has since been shown to be an artifact (107). 

Chloroform adducts 190a and 190b of berberine (15) and palmatine (64) are well known. Column chromatography of palmatine-chloroform 190b on silica gel with chloroform-methanol gave saulatine (192) (Scheme 34). This alkaloid and its analog puntarenine (191) had been isolated from Abuta bullata (108) and B. actinacantha (109), respectively, but have now been shown to be artifacts (107). 

Indenobenzazepines have been used as key intermediates for synthesis of rhoeadine, protopine, phthalideisoquinoline, and spirobenzylisoquinoline alkaloids. Several new alkaloids possessing an indenobenzazepine skeleton have been isolated, and they are presumably biosynthesized from proto-berberine alkaloids. 

Fig. 10.8 Selected cDNAs isolated in recent years that encode enzymes involved in the biosynthesis of various classes of isoquinoline alkaloids. 6-OMT, norcoclaurine 6-0-methyltransferase 23 CYP80A1, berbamunine synthase 19 CYP80B1, (S)-A-methylcoclaurine 3 -hydroxylase 20 CPR, cytochrome P-450 reductase 29 4 -OMT, (5)-3 -hydroxy-A-methylcoclaurine 4 -0-methyltransferase 30 BBE, berberine bridge enzyme 12 SalAT, salutaridinol 7-O-acetyltransferase 28 COR, codeinone reductase.25...

Gentry EJ, Jampani HB, Keshavarz-Shokri A, Morton MD, Velde DV, Telikepalli H, Mitscher LA, Shawar R, Humble D, Baker W. (1998) Antitubercular natural products Berberine from the roots of commercial Hydrastis canadensis powder. Isolation of inactive 8-oxotetrahydrothalifen-dine, canadine, beta-hydrastine, and two new quinic acid esters, hycandinic acid esters-1 and -2. J Nat Prod 61 1187-1193. 

Most other alkaloids shown to have AChE inhibitory activity have been isolated from plants used in traditional medicine. Coptis chinensis Franch has been used in TCM for several conditions including age-related cognitive and memory decHne. Some alkaloids found in this species e.g. berberine (43), coptisine (44) and palmatine (45) are reported to also be antiChE. Coptis chinensis extract improved a scopolamine-induced learning and memory deficit in rats and this is likely to be due to the alkaloids present thus raising ACh levels. Berberine (43) has been shown to selectively inhibit AChE compared with Bu ChE and it has been shown to improve scopolamine-induced amnesia in rats. ... 

Biosynthetic research relating to the isoquinoline family was extremely successful, with such important members as morphine [3, 14], codeine [3, 15] or berberine [3, 14,16-18]. Extensive efforts have provided details pertaining to multiple sets of enzymes participating in the biosynthesis of the alkaloids above, in many cases with the help of plant cell suspension culture techniques. Since 1988, when the breakthrough in cloning of cDNA from alkaloid biosynthesis occurred [19, 20], a significant number of enzymes known from the indoles and isoquinolines biosynthesis have been isolated, their biochemical properties described and the majority of their corresponding cDNAs cloned and functionally over-expressed in non-plant hosts such as Escherichia coli, yeast or insect cells. 

The isolation of the cDNAs encoding the enzymes involved in diverse isoquinoline alkaloid formation in plants and microorganisms allowed the first metabolic engineering routes to be developed and paved the way for new ways of future production of isoquinoline alkaloids. For instance, transgenic opium poppy plants were created in which codeinone reductase was suppressed by RNAi, resulting in the substitution of morphine synthesis with the non-narcotic precursor reticuline [110]. In a similar approach, RNAi suppression or overexpression of salutaridinol 1-0-acetyltransferase in opium poppy led to accumulation of salutaridine or increase of morphine, codeine and thebaine content [111], suppression of the BBE led to accumulation of berberine in California poppy cells [112],... 

Berberine was isolated for the first time from Berberis vulgaris L. (472). The pharmacological properties of berberine resemble those of... 

Cryptopine was isolated by Smiles (579) from opium in 1867. Its effect (580) is in many respects similar to that of papaverine and berberine. In dogs it produces hypotension, inhibition of cardiac activity, stimulation of respiration, inhibition of faradization of the vagus, and decrease in the oculocardiac reflex in rabbits, it produces relaxation of the skeletal muscle (581). For guinea pigs the LD100 s.c. was found to be 160 mg/kg (582). Mercier el al. (583, 584) reported the effect of cryptopine on the intestine, the nervous system, blood pressure, cardiac activity, and respiration to range between that of papaverine and berberine. 

This is the name given to an alkaloid (mp 200-201°) isomeric with protopine, isolated from Zanthoxylum conspersipunctum Merr. (146), whose structure (157) has been confirmed by a synthesis. The reaction sequence, beginning with the corresponding berberine, was essentially that described in the original protopine synthesis (147). 

Three new alkaloids that can be regarded as 10-aza-berberines have been isolated from Alangium lamarckii, namely alangimarine (71 R = H=CH2), alangimaridine (72), and alamarine 171 R = CH(OH)Mel. Their structures were deduced from... 

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