Bond Cleavage Reactions of Protoberberines

The C—N bond cleavage is a fundamental and key reaction in skeletal rearrangements of protoberberines. The remaining two cleavages, that is, of the C—C and C—O bonds, are not always essential to transformation. 

This recyclization reaction has been skillfully utilized for stereospecific labeling at C-13 of tetrahydroberberine with tritium or deuterium for biosynthetic studies of ophiocarpine (20). Base A- and B-type products have 

The stereochemistry of corydalic acid methyl ester (8) was confirmed by correlation with the Hofmann degradation product of mesotetrahydro- 

Reaction under solvolytic conditions such as in ethanol or aqueous tetrahydrofuran caused exclusive C-14—N bond cleavage and introduction of an ethoxyl or hydroxyl group at C-14, giving 30 in excellent yields (34). Addition of a base such as magnesium oxide to the reaction mixture was found to be useful to avoid the recovery of the starting material as the hydrobromide (35). The reaction was used for a synthesis of protopine alkaloids (Section V,E,5). 

Although C—O bond cleavage is of little importance for transformations of protoberberines to other types of alkaloids, the selective C—O bond cleavage reaction provides access to naturally unabundant or nonnatural protoberberines from naturally abundant protoberberines such as berberine. 

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