From Papaverine

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). 

The optical resolution of pavine (I) (obtained by synthesis from papaverine) and Trdger s base (II) on a microcrystalline triacetylcellulose (MCTC) column has been demonstrated [20]. 

A synthesis of sevanine (16) by Bischler-Napieralski ring-closure of the amide (17) followed by hydrogenolysis and dehydrogenation has been reported.27 The alkaloid has also been prepared from papaverine by demethylation and methyl-enation with dichloromethane.27... 

The benzylic carbanion from papaverine has been converted into a variety of substituted bases of general structure (30) by treatment with alkyl halides, aminoalkyl halides and ethyl acrylate (A. Buzas and G. Lavielle, Patent, Chem.Abs., 1981, 95, 25378, 150978) and the ion from dihydropapaverine (31) has been found to react with cyclohexan-1,2-dione in the presence of excess base to give the spiro ketone (35) presumably via the intermediates (32), (33) and (34). 

As mentioned above, quaternary papaverinium salts were reduced to DL-laudanosine (XIII) under a variety of conditions (17, 28, 29, 30, 76). Alternatively, tetrahydropapaverine may be treated with methyl iodide to give DL-laudanosine hydriodide (85). The route from papaverine via protopapaverine and DL-laudanosoline 3, 4-dimethyl ether (LVII) has already been mentioned. Methylprotopapaverinium iodide can be reduced to DL-codamine (XXII), which can be methylated to DL-laudanosine. Not only DL-codamine but its three phenolic isomers (p. 53) can be converted to DL-laudanosine by the action of diazomethane (33, 83, 86). 

The two bases described in this section have not been found in plant materials, but are formed by certain chemical reactions from papaverine or laudanosine. 

Condensation would obviously take place at either the 2- or the 6-position of the benzyl ring, but it was possible to isolate both the meso- and racemic corydalines from the reaction mixture. The tetrahydroxy base (LXII) was obtained from its tetramethyl ether, which was prepared from papaverine. For this purpose papaverine was condensed with formaldehyde (256) and the methylenepapaverine so formed was reduced first ( atalytically to methylpapaverine (257) and then elei trolytically to the tetrahydro base— presumably a mixture of the meso- and racemic forms. 

The synthesis of 13-hydroxylated tetrahydroprotoberberines from norphthalideisoquinolines has been achieved. Catalytic reduction of the phthalide-isoquinoline 32, derived from papaverine (see Sec. 24.2.3), afforded a separable mixture or erythro- and /Areo-norphthalideisoquinolines. Base-catalyzed lacta-mization followed by lithium aluminum hydride reduction of the threo-nov and rj fAro-norphthalides yielded the 13 - and 13a-hydroxytetrahydroprotober-berines, respectively. The hydroxylactam derived from the / r o-norphthalide tends to dehydrate readily to the oxoprotoberberine system (see Scheme 19.4). ... 

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