Berberine-chloroform

Scoulerine (145 R = H), the main constituent of Argemone albiflora, had not been previously obtained from Argemone species.The previously named alkaloid HF 1 isolated from Hunnemannia fumariaefolia was found to be identical with ( —)-scoulerine. The co-occurrence of (— )-tetrahydropalmatine (145 R = Me) and (-f )-armepavine in Argemone turnerae has been established for the first time.The isolation and characterization of two artefact alkaloids, berberine chloroform (146 R + R = CH2 R = H,CCl3) and palmatine chloroform (146 R = R = Me, R = H,CCl3), from Berberis lycium have... 

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). 

The cycloberbine 339 derived from coptisine (65) was reduced with lithium aluminum tri-tert-butoxyhydride to afford the trans-alcohol 340 along with a small amount of the cis-alcohol (Scheme 62). Treatment of 340 with ethyl chloroformate effected C-8—N bond cleavage and simultaneous oxyfunc-tionalization at C-8 with the desired stereochemistry to produce the oxazolidinone 341. This was hydrolyzed with potassium hydroxide and then underwent N-methylation to give ( )-ochrobirine (343). Similarly, the ochrobirine analog 344 was also obtained from berberine (15) (171). 

Ring D inversion seems to be a crucial step in biogenetic transformations of protoberberines to related alkaloids such as rhoeadine, retroprotoberberine, spirobenzylisoquinoline, and indenobenzazepine alkaloids. 8,14-Cyclober-bin-13-ol 478 derived from berberine (15) was successively treated with ethyl chloroformate, silver nitrate, and pyridinium dichromate (PDC) in dimethyl-formamide to give the keto oxazolidinone 479 (Scheme 98). Heating of 479 with 10% aqueous sodium hydroxide in ethanol effected hydrolysis, retro-aldol reaction, cyclization, and dehydration to provide successfully the... 

Berberine reacts with dichlorocarbene in chloroform to give the penta-chloro-compound (64), which is hydrolysed to the aldehyde (65 R = CHO) by aqueous acid this can be reduced to the alcohol (65 R = CH2OH) by sodium... 

Fumaricine (90) has been synthesized from the berberine (87) by photolytic transformation into (88) followed by conversion into (89) by ethyl chloroformate, catalytic removal of the chlorine, and reduction with lithium aluminium hydride.163... 

Secondary metabolites produced by plant cell culture are commonly accumulated in the cells. With few exceptions such as Capsicum frutescens, Thalictrum minus (9) and Vanilla planifolia (Knorr, D. and Romagnoli, L., Univ. of Delaware, unpublished data) cultures, which release valuable compounds such as capsaicin, berberine and vanillin, respectively, into the medium, procedures to induce product release are required to develop continuous production processes. Reported permeabilization methods include treatment with dimethylsulfoxide (DMSO), isopropanol, toluene, phenethyl alcohol or chloroform (9, 28). But as Fontanel and Tabata (9) pointed out, such treatments with organic solvents are severe and other methods of permeabilization need to be developed. 

A two-phase solvent system composed of chloroform-methanol-dilute inorganic acid has been used for the separation of a variety of alkaloids including isoquinoline alkaloids, naphthyl-tetrahydroisoquinoline alkaloids, fla-vonoid alkaloids, pentacyclic aromatic alkaloids, diterpenoid alkaloids, aporphine alkaloids, etc. The following example illustrates a typical systematic solvent selection for the separation of palmatine, berberine, epiberberine, and coptisine from the crude alkaloids of Coptis chinensis Franch by analytical HSCCC. In Fig. 1, nine chromatograms are arranged in such a way that the effects of the concentration of HCl (0.3-0.1 M) and the relative volumes of methanol (4 3 2-4 1.5 2, v/v) on the separation of alkaloids from C. chinensis Franch are each readily observed. As the concentration of HCl is reduced from 0.3 to 0.1 M in the solvent system, the retention time... 

The conversion of berberines into spirobenzylisoquinolines has been examined in detail. As described in section 8 photolysis of the betaines (190, R=H) and (190, R=Me) affords the aziridines (198, R=H) and (198, R=Me). Treatment of (198, R= Me) with methyl iodide is accompanied by Hofmann degradation to give the ochotensine analogue (307, R=Me) and treatment with ethyl chloroformate results in a von Braun degredation... 

The free bases are soluble in lipophilic organic solvents, like chloroform. The different solubility for bases and salts is used for isolation and purification. Alkaloids are generally colourless solid materials. Some alkaloids that do not contain oxygen, like coniine, nicotine and sparteine, are liquid, and berberine and chelidonine are intensely yellow. Several alkaloids, e.g. strychnine and quinine, have a very bitter taste. Alkaloids give precipitates with heavy metals like mercury and bismuth. DragendorfPs reagent is used to show the presence of alkaloids. 

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). 

Palmatine forms addn products with acetone and chloroform, as does berberine. 

A simple method of isolation of berberine has been described, as has its rapid determination in the crude plant material (665, 666). Confirmatory evidence has been provided again that, on extraction, the protoberberine bases in chloroform form additive products and the corresponding 8-oxyberberine derivatives (667). 

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°. 

Exploitation of alkaloid release for production purposes requires further studies with respect to timing of the induction of alkaloid biosynthesis, secretion of the edkaloids, and regrowth of the cells. Electroporation has been shown as a possible way to permeabilize T. rugosum cells however, in obtaining complete release of the alkaloids, the cells lost their viability (549). The use of various chemical agents for permeabilization (chloroform, DMSO, Triton X-lOO, hexadecyltrimethylammonium, phen-ethyl alcohol) gave similar results. At concentrations necessary to release berberine from the vacuole, the cells did not grow anymore after the treatment (87). 

The P. a. are readily soluble in ethanol, chloroform, and ether. Berberine is a toxic yellow pigment occurring in Berberis and Mahonia species. Silk, cotton, and leather can be dyed with berberine. It has also been the subject of intensive pharmaceutical research and exhibits many interesting properties including stimulation of respiration, hypotensive and convulsive activities. It is an inhibitor of choline esterase, tyrosine... 

Among the most frequently used organic solvents is chloroform, used for the determination of many analytes in various samples free cyanide and thiocyanate ions in human saliva chlorophenols in urine and Bi(III), ethambutol hydrochloride, diclofenac, phenothiazine derivatives, imipramine, warfarin, flufenamic acid, and ethylmorphine in pharmaceutical preparations. Another proposed solvent is dichloro-ethane, used for the determination of bromhexine in serum and imipramine, ambroxol, berberine, bromhexine, neostigmine, 8-chlorotheophylline, and diphenhydramine in pharmaceutical samples. 

This formula was confirmed by Haworth and Perkin s synthesis of a-aZZocryptopine from herberine, the first application of a process, of which examples have heen given already in the syntheses of cryptopine (p, 298) and protopine (p. 801) by the same authors. Anhydrotetrahydromethyl-berberine (I cf. base (a), p. 846) in dry chloroform was added to a solution of perbenzoic acid in ether cooled below 5°. The amine oxide,... 

Isoquinoline alkaloids can be subdivided into two groups. Those alkaloids which preserve the isoquinoline moiety and those which have a reduced ring structure, the tetrahydroisoquinolines. Papaverine, a smooth muscle relaxant, possesses the isoquinoline moiety. In chloroform, papaverine fluoresces at Af = 347nm (Agx=315nm). The addition of some trichloroacetic acid to this protonates the isoquinoline moiety and causes a shift in absorption and fluorescence peaks (Agx = 415nm 2f = 452nm). Berberine is an isoquinoline alkaloid which has a quaternary nitrogen with hydroxide as the standard counterion. In ethanol it has excitation maxima of... 

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