Berberine oxidation

Dehydrocorydaline, C22H2304lSk (Items 8,14, 31 list, pp. 170-2.) This alkaloid is formed by the gentle oxidation of corydaline.It is a yellowish crystalline powder, m.p. 112-3° (dec.) the hydrochloride, B. HCl. 4H2O, forms yellow leaflets hydriodide, B. HI. 2H2O, small yellow needles aurichloride, B. HAUCI4, red-brown needles, m.p. 219°. Like berberine,... 

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. 

On treatment with aerated sodium in liquid ammonia, tetrahydroproto-berberine JV-oxides (35a and 35b) afforded the C-14—N bond cleavage products 36 and 37 (Scheme 8) (37). The same trans IV-oxides also gave the C-14—N cleavage products 38 and 39 on photolysis (33). 

Although several oxidative C—C bond cleavages have been observed, the only method useful for transformation is C-8—C-8a bond cleavage. Treatment of berberine (15) with m-chloroperbenzoic acid in dichloromethane in the presence of sodium bicarbonate at - 78°C gave polyberbine (66) and N-formylnoroxyhydrastinine (69, R1 + R2 = CH2) in 20 and 15% yield, respectively (Scheme 16) (54). Similar treatment of palmatine (64) and coptisine (65) led to polycarpine (67) and the enamide 68, respectively, in 40-50% yield (55). The yield of polyberbine was improved to 76% when.the oxidation was carried out in tetrahydrofuran in the presence of sodium hydride however, the yields of 67 and 68 could not be improved under the, same reaction conditions (56). The products were used for synthesis of tetrahydroprotoberberine (Section V,I,5) and aporphine alkaloids (Section V,J,3). 

Introduction of a hydroxyl group into the protoberberine skeleton was successfully carried out by the hydroboration-oxidation method. Dihydro-berberine (90) was converted to ( )-epiophiocarpine (91) as a major product along with ( )-ophiocarpine (92) (Scheme 22) (71). 5-Hydroxyprotober-berines 94 and 95 were obtained from the 5,6-dehydro compound 93 (50) synthesized from papaverine via 54 (72). 

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). 

A biomimetic synthesis of benzo[c]phenanthridine alkaloids from a protoberberine via the equivalent of a hypothetical aldehyde enamine intermediate has been developed (130,131). The enamide 230 derived from berberine (15) was subjected to hydroboration-oxidation to give alcohol 231, oxidation of which with pyridinium chlorochromate afforded directly oxyche-lerythrine (232) instead of the expected aldehyde enamide 233. However, the formation of oxychelerythrine can be rationalized in terms of the intermediacy of 233 as shown in Scheme 41. An alternative and more efficient... 

Shammaet al. (144-146) utilized Hofmann degradation of 8-benzyltetrahy-droprotoberberine for selective C-8—N bond cleavage (Section II,A,1). Benzylidene products 17 and 271, derived from berberine (15) and coptisine (65), were subjected to Lemieux-Johnson-Pappu oxidation to provide (+)-canadaline (272) and ( )-aobamine (273), respectively, the latter of which was... 

The spirobenzylisoquinoline 171b derived from berberine (15) (Section IV,A,1) was oxidized with m-chloroperbenzoic acid to the /V-oxide 389, which was treated with trifluoroacetic anhydride to afford dehydrohydrastine (370) in 56% overall yield (Scheme 71) through the Polonovski reaction (187). Holland et al. (188,189) reported the reverse reaction from dehydrophthalides to spirobenzylisoquinolines, namely, 370 was reduced with diisobutylalu-minum hydride to give a mixture of two diastereoisomeric spirobenzylisoquinolines 320 and 348 via the enol aldehyde. This reaction was applied to synthesis of various spirobenzylisoquinoline alkaloids such as (+)-sibiricine (352), ( + )-corydaine (347), (+ )-raddeanone (354), ( )-yenhusomidine (359), (+ )-ochrobirine (343), and ( )-yenhusomine (323). 

Another interesting conversion of a protoberberine to a rhoeadine skeleton was developed by Murugesan et al. (100). The ketol 176 obtained easily from berberine (15) (Section IV,A,2) was oxidized with sodium periodate to the keto lactone 451, which was transformed to the rhoeadine analogs 452 and 453 by known methods (Scheme 91). Their stereochemistry at the anomeric carbon was not fully clarified. 

Oxidative conversion of palmatine, berberine, and coptisine to polycarpine, polyberbine, and its analog was described in Section II,B. These products were further transformed to aporphine alkaloids having a phenolic hydroxyl group at C-2 in the bottom ring (55). Hydrolysis with concomitant air oxidation of polyberbine (66) furnished 3,4-dihydrorugosinone, which was further air-oxidized in ethanolic sodium hydroxide to give rise to rugosinone (501) (Scheme 105). Successive reduction of the enamide 68 with lithium aluminum hydride and sodium borohydride afforded a mixture of ( )-norledecorine and (+ )-ledecorine (502). N-Methylation of the former with formaldehyde and sodium borohydride led to the latter. 

In a novel synthetic route involving the transformation of a tetrahydroproto-berberine nucleus to a pavine skeleton (Scheme 10) 119), canadine methiodide (67), was subjected to Hofmann degradation to yield styrene 68. This compound was successively oxidized with osmium tetraoxide-sodium periodate and the... 

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... 

Berberine can be oxidized by nitric acid to berberidic acid (82), which forms two isomeric monomethyl esters these can be reduced first to the isomeric unsaturated lactones (83) and (84) and further to saturated lactones and to cis- and trans-diols (85). Hydrogenation of berberidic acid diester affords an allo-hexahydro-compound, which is isomerized by base to a normal hexahydro-compound. Oxidation of the lactone (84) with mercuric acetate affords the aromatized lactone (86).95... 

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