Berberine irradiation

Oxidation of berberine (15) with potassium ferricyanide followed by treatment with sodium hydroxide afforded oxybisberberine (130) (30%), the structure of which is still unknown (Scheme 27). The product was treated with 10% methanolic hydrogen chloride to give 8-methoxyberberinephenolbetaine (131) (93%) and 15 (77%) (88,89). Alternatively, irradiation of 15 in methanol in the presence of sodium hydroxide and Rose Bengal in a stream of oxygen gave the tetramethoxyketone 132 (59%), which was aromatized to 131 (99%) by removal of methanol on heating in methanol (90,91). 

B. Das et al. have further demonstrated the use of microwave irradiation in the modification of natural products, by converting Berberine into Berberru-bine (Scheme 29) [112]. Berberine, the quarternary alkaloid from Tinospora... 

Cava and Havlicek (108) found that irradiation of the A-benzoate 129 in the presence of iodine and cupric acetate yielded the 13-phenyloxoproto-berberine 130 exclusively. 

The similar conversion of dihydroepiberberine (122) to ( )-fumaritrine (127) was achieved by the same author (Scheme 25). Epiberberinephenol-betaine (123), derived from 122 by oxidation with w-chloroperbenzoic acid, was irradiated in methanol with a high-pressure mercury lamp to give the aziridine 124. Reduction of 124 with sodium borohydride in methanol yielded the alcohol 125 stereoselectively, which was further converted to the d -benzindenoazepine 126 by treatment with j7-toluenesulfonic acid in methanol, followed by methylation with methyl iodide. Successive mesyla-tion of 126 and reduction of the mesylate afforded ( )-fumaritrine (127) in 71% yield. Thus the conversion of berberines to benzindenoazepines was successfully accomplished by the formation of aziridine derivatives as key intermediates by photochemical valence tautomerization. 

An efficient conversion of berberine to a rhoeadine via an aziridine was also reported independently by Shamma (Scheme 28). Irradiation of ber-berinephenolbetaine (136), containing aqueous formaldehyde and a little rose bengal, afforded the indenobenzazepine derivative (138) (60%) via the ketoaziridine 137. Reduction of 138 with sodium cyanoborohydride in the presence of dry methanolic hydrogen chloride afforded the keto alcohol 139, periodate oxiiiation of which furnished the y-lactone 140. Sodium borohy-dride reduction of 140, followed by acid treatment, gave the lactone 141, which was further converted to the c -rhoeadi ne derivative 142 by reduction and 0-methylation. 

The isolation of the effective compositions from some traditional Chinese herbs under influence of ultrasound was reported [71], The compounds Helicid (4-for-mylphenyl-allopyranoside), Berberin Hydrochloride, and Bergenin could each be isolated from different plant materials using ethanol at room temperature under the influence of sonication. Ultrasonic irradiation reduced the temperature and time required for the process, thereby increasing the efficiency of extraction. The products contained fewer impurities and the ultrasonic process appeared to involve simpler technology. 

Protopine, allocryptopine, and cryptopine when irradiated in ethanol or chloroform under a nitrogen atmosphere gave yields of 23% to 76% of coptisine, berberine, and epiberberine. The reaction rate in chloroform was greater than in ethanol (or methanol) and the yields were better 169). 

The aziridine (67), formed by irradiation of berberine betaine, on treatment with formaldehyde, gives the base (68), which on reduction with sodium cyanoborohydride affords a cis-glycol that is... 

Nonsensitized photochemical oxidation of dihydrodibenzo[a,5 ]quinolizinium compounds such as berberine (102) in the presence of nucleophilic reagents affords isoquinoline lactam aldehydes (103) (Scheme 13) <84H(22)10l>. A mechanistic proposal <81H(16)1735> involving the intermediacy of the dihydroberberine (104) was rejected on the basis of the results of direct irradiation of this compound. Participation of singlet oxygen was also excluded. 

In its APT spectrum, berberine (1) shows the anticipated two methyl, three methylene, six methine and nine quaternary carbon atoms. The three methylene signals at 6 26.35, 55.19 and 102.07 were assigned to C-5, C-6 and the 2,3-methylenedioxy carbon, respectively. CSCM ID irradiation of the C satellites of H-1, H-4, H-8, H-11, H-12 and H-13 resulted in the magnetization transfer to their carbon atoms appearing at S 105.43, 108.41, 145.42, 126.69, 123.53 and 120.18, respectively. The nine quaternary carbon atoms whose assignment was the focus of the study could be subdivided as... 

An alternate preparation of 8-methoxyberberinephenolbetaine proceeds through irradiation of berberine in methanol containing rose bengal and sodium methoxide, with a stream of oxygen. A precipitate is thus obtained which upon recrystallization from methanol yields orange-colored crystals of 8-methoxy-berberinephenolbetaine. Borohydride reduction then affords mostly ophio-carpine and a much smaller yield of epiophiocarpine. ... 

Apart from the low toxicity of berberine against normal tissues, it has also been showed that this molecule exerts a protective effect on lung tissue during irradiation [187]. 

Hur JM, Hyun MS, Lim SY, Lee WY, Kim D (2009) The combination of berberine and irradiation enhances anti-cancer effects via activation of p38 MAPK pathway and ROS generation in human hepatoma cells. J Cell Biochem 107 955-964... 

---