Berberine betaine

Betaines of 13-hydroxyberberine and its analogues of general type (190) are easily prepared. Berberine betaine (190, R=H) is obtained by the oxidation of berberine-acetone (191) with potassium permanganate, in a process that invoves a retro-Mannich loss of acetone, and methoxyberberine betaine (190, R= OMe) results from the controlled photo-oxidation of berberine. Other analogues can be prepared by the oxidation of dihydro-and 8-alkyldihydro-berberines. Both (190, R=H) and (190, R= OMe) can be reduced to a mixture of ophiocarpine (192) and the C-13 epimeric epiophiocarpine (M. Hanaoka. C. Mukai and Y. Arata, Heterocycles, 1977, 895). Photo-oxidation of the... 

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... 

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... 

The yellow-orange Neooxyberberine (52) (9,10-dimethoxy-5,6-dihydro-[1,3]dioxolo[4,5-g]isoquino[3,2-u]isoquinolinium-l 3-olate phenolbetaine of Berberine , 13-hydroxyberberinium phenol-betaine ) was already... 

Oxidation of berberine (49) with hot dilute nitric acid yields berberidic acid (220) (58MI1) which can form a cross-conjugated and a pseudo-cross-conjugated mesomeric betaine on deprotonation as shown in Scheme 72. 

The first conversion of protoberberines to phthalideisoquinoline alkaloids was achieved by Moniot and Shamma (88,89). 8-Methoxyberberinephenol-betaine (131), derived from berberine (15) (Section III,B,2), is an attractive compound having a carboxyl group masked as an imino ether in ring B. The masking was uncovered by hydration with water-saturated ether to furnish dehydronorhydrastine methyl ester (367) (Scheme 65). On N-methylation (68%) and subsequent sodium borohydride reduction (90%), 367 provided (+ )-/ -hydrastine (368) and ( )-a-hydrastine (369) in a 2 1 ratio. Compound 367 was converted to dehydrohydrastine (370), which also afforded 368 and 369 by catalytic hydrogenation. 

Berberine hydrochloride (2H2O) [633-65-8] M 371.8, m 204-206°(dec). Crystn from water gives the dihydrate. The anhydrous salt may be obtained by recrystn from EtOH/Et2O, wash with Et2O and dry in a vacuum. It has pKa 2.47. The iodide has m 25 )°(dec) (from EtOH). [IR JCS 113 503 1918 2036 7969]. Betaine [107-43-7] M 117.1, m 301-305°(dec) (anhydrous). Crystd from aqueous EtOH. 

The alkaloid berberine (360) is the source of two interesting mesomeric betaines (Scheme 14).256.257 Reaction with acetone gives 8-acetonyldihydro-berberine (361) which is oxidized to the bridged compound 362 (neooxyber-berineacetone) by potassium permanganate. 258.259 Treatment of compound 362 with hot dilute mineral acid followed by base gives the betaine 364 which... 

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... 

Berberine has been converted into a mixture of a- and /3-hydrastines, in the proportions 1 2 oxidation with potassium ferricyanide produced dimeric oxy-bisberberine, which with methanolic hydrochloric acid yielded the betaine (91). Hydration of this, followed by N-methylation, yielded the keto-ester (92), which gave a- and /3-hydrastines on reduction with sodium borohydride and subsequent hydrolysis.100 The photo-oxidation of tetrahydroberberine methiodide to allo-cryptopine has been reported.101... 

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. 

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... 

Berberine alkaloids synthesis steps, 295-297 Betaines in Wittig olefinations, 29-30 Bicyclic compounds. See Oligocyclic compounds Bicyclic hydrocarbon derivs. pr., 192 Bicyclo[4.1.0]hepta-2,4-dienes rearr., 334 Bicyclo[2.2.1]heptane derivs. pr., 192... 

A patent that covers the oxidation of berberines to oxybisberberines with potassium ferricyanide, and the conversion of these into 13-methoxyoxyber-berines, e.g. (72), has been reported. Conditions for the conversion of the oxybisberberines into the 8-methoxyoxyberberine betaine (73) have previously been reported (Vol. 8, p. 105). 

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