13- Hydroxylated tetrahydroprotoberberines

The Mannich cyclization has also been used in the preparation of 13-hydroxylated tetrahydroprotoberberines. Air oxidation of 3,4-dihydropapa-verine gave 3,4-dihydropapaveraldine which was reduced with sodium boro-hydride to furnish only one a-hydroxylated tetrahydrobenzylisoquinoline. Mannich cyclization of this material with formalin gave a 60% yield of 13a-hydroxyxy lopinine. ... 

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). ... 

Tetrahydroprotoberberines (59) having a phenolic hydroxyl group were heated in trifluoroacetic anhydride in a sealed tube to afford the indene derivatives (60) after treatment with methanol (Scheme 14) (57). The products formed through both C-14—N and C-8—N bond cleavage followed by ring closure. 

The presence of three methoxyl groups and a phenolic hydroxyl group in corydalmine indicated the extended molecular formula Ci7Hi4N(0Me)30H, and its formulation as a tetrahydroprotoberberine base was suggested from the UV-spectrum X 284 my, log e 3.56). The... 

Protoberberines were reduced with NaB H4. The tritiated (S)-tetrahydroproto-berberines were methylated by the (S)-tetrahydroprotoberberine-cis-N-methyl-transferase. If the (S)-cis-N-methyltetrahydroprotoberberines are hydroxyl-ated a H-release into water can be measured. 

Dehydroprotoberberinium salts may be used as intermediates for the introduction of substituents at the C-5 position of tetrahydroprotoberberine bases. Two-step reduction of dehydronorcoralydine leads to the enamine 51 which can be C-acylated as in 52, or hydroborated and oxidized to give a separable mixture of diastereomeric C-5 hydroxylated tetrahydroprotoberbines ... 

Several new suggestions concerning the biogenesis of the rhoeadines have appeared. Using Papaver bracteatum Lindl. plants, it has been demonstrated that [N- CHa, 8- C]-( )-tetrahydropalmatine methiodide is incorporated with high efficiency into alpinigenine. A mechanism was therefore proposed which involves C-14 hydroxylation of the quaternary tetrahydroprotoberberine salt, followed by cleavage of the bond between N-7 and C-14. ... 

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