Bisbenzylisoquinoline alkaloids reduction

Ceric ammonium nitrate appears to be a valuable reagent for dehydrogenation of bisbenzylisoquinoline alkaloids. For example, oxidation of tetrandrine (48) with 8 mol of this reagent in buffered HOAc, followed by NaBH4 reduction of the intermediate imine 381, gave a 95% yield of diamine 382, as well as the crystalline diol 383. Similarly successful results were obtained with heman-dezine (24a) and O-methylmicranthine (384), the latter demonstrating that this procedure is compatible with secondary amino groups. Berbamine (364),... 

Methods of synthesis of bisbenzylisoquinoline alkaloids have been reviewed83 and the use of electrochemical methods for the reduction of the dihydro-isoquinolinium salts that result from Bischler-Napieralsky ring-closures in the synthesis of, for example, espinidine has been studied.84... 

The metal-ammonia reductive cleavage of the bisbenzylisoquinoline alkaloids has continued over the past eight years to be instrumental in unraveling their stereochemistry. It has provided the means of establishing not only the relative stereochemistry of these alkaloids but also their absolute configuration. 

Oxidation with ceric nitrate has been developed as a new degradative procedure in the study of bisbenzylisoquinoline alkaloids. This reagent splits lau-danosine to veratric aldehyde and the N-methyl-6,7-dimethoxy-3,4-dihy-droisoquinolinium ion, isolated as veratryl alcohol and N-methyl-3,4-dimethoxytetrahydroisoquinoline after reduction. In the same way, tetrandrine, hernandezine, and O-methylmicranthine have been degraded to the bis-tetra-hydroisoquinolines (48 R = H), (48 R = OMe), and (49), the second product in each case being the diphenyl ether (50). ... 

L-( + )-i T-Methylcoclaurine, C19H23NO3 (XIII), has been isolated from Cocculus laurifolius DC. (Menispermaceae) and named coclanoline (33) (vide infra). D-( — )-iV -Methylcoclaurine was isolated from Phylica rogersii Pillans (Rhamnaceae) (34). Both enantiomers have been obtained in many cases by reductive cleavage with sodium in liquid ammonia of bisbenzylisoquinoline alkaloids (11, 12). 

Both (+)- and (— )-0-methylarmepavine have been isolated by reduction with sodium and liquid ammonia of several bisbenzylisoquinoline alkaloids (11, 12). They have also been obtained in a series of reactions leading to the determination of the absolute configuration of armepavine which have already been considered in detail (Section II, H). The rotation of L-( -I- )-0-methylarmepavine was determined by Tomita and Kunitomo (10) in several solvents of increasing polarity they observed an increase in the values in going from benzene to iV-hydrochloric acid (mp 61°-62° [ ]"d —6.9° in benzene —6.1° in pwidine [ ] [[ +86.3° in CI3CH ... 

D-( — )-Laudanidine and d-( + )-laudanidine were also obtained by Tomita and Kunitomo (10) by reductive fission of the corresponding D-( —)- and L-( + )-laudaiiosines with sodium in liquid ammonia (Section III, F). Reduction of bisbenzylisoquinoline alkaloids by the same method have yielded laudanidine from some of them (— )-laudanidine from 0,0 -dimethylcurine (38) and (+ )-laudanidine from fetidine (132). The latter enantiomer was also produced by diazotization of the (+ )-amino base (XXXV) and decomposition of the diazo compound in the presence of fluoboric acid (9) (Section II, H). 

---