Berberine-acetone

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 chemistry of protoberberine-acetone adducts has been reconsidered within the context of ease of alkylation and oxidation. Naruto and his students have reported that reactive alkyl halides such as methyl iodide react with berberine-acetone to yield, in addition to the expected berberine and 13-methylberberine, the bridged derivatives 38 and 39. ... 

Berberine-acetone when subjected to mild permanganate oxidation is converted to neoxyberberine-acetone and to the lactamic acid 43 reminiscent of Perkin s berberal. ... 

The above sequence has been adapted to a synthesis of the deoxy analog 12 of corynoline. Berberine-acetone, easily prepared from berberine, was converted to the enamine 9 whose photolysis yielded two pseudobases, 10 and 11. These could be reduced with sodium borohydride to the angularly methylated benzophenanthridine 12 (see Scheme 21.4). ... 

Karachine (505) (253), the first natural protoberberine incorporating an acetone unit, was synthesized from berberine (15) (254). Heating of 15 with siloxydiene 503 in dimethyl sulfoxide afforded karachine (505) in 66% yield through Mannich condensation, intramolecular Michael addition, and then further Mannich condensation via 504 (Scheme 106). 

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... 

A closely related reaction with berberines has been known80 for some time. Palmatine [(41) R = OMe] condenses with acetone to yield the 1,2-dihydroisoquinoline derivative [(55) R = OMe] which, with methyl iodide, followed by acid-catalyzed removal of the acetone residue, yields 56. Reduction then gives corydaline [(57) R = OMe]. Dihydroberberine (34) is alkylated by methanol in a similar reaction... 

R = OH). Although similar oxidation of acetone-palmatine gives an 8,13a-propanoberberine analogous to (119 R = OH, R = H), 13-methyl-acetone-berberine (115 R = Me) gives mainly the lactam (121) together with small amounts... 

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

When berberine is the chief alkaloid in a plant extract its isolation is conveniently effected by making use of the sparing solubility of its sulfate in dilute sulfuric acid. The hydrochloride, hydriodide, and nitrate are easily recrystallized from water or precipitated from acetic acid solutions on the addition of the appropriate ions in the form of salts (182). The phosphate (183) is a bright yellow, non-deliquescent crystalline substance soluble in 14.3 parts of water at 16°. Berberine can be purified through its addition compound with acetone (184, 185, 186). 

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