Bisbenzylisoquinoline alkaloids synthesis

Bisbenzylisoquinoline alkaloids, synthesis of 80UK1617. Bisbenzylisoquinolines, relation between optical rotation and steric struc-... 

The format follows that of the earlier review. The subject of synthesis, however, which formerly constituted a separate chapter, is included in this work, and other coverage has been expanded, particularly in the areas of plant biochemistry and pharmacology. The tabulation of all known bisbenzylisoquinoline alkaloids has been revised and updated. A section listing other major review articles on these alkaloids is also included, and the reader may wish to consult some of these for extensive physical data. In keeping with the original purpose of this treatise, we have tried for a comprehensive overview, with strong emphasis on the specific chemistry of the bisbenzylisoquinoline alkaloids, rather than an exhaustively detailed presentation. 

This section consists primarily of total synthesis work. Most partial syntheses are to be found in Sections II and IV, and only those not previously discussed or those of particular interest are considered here. The last decade has produced relatively few new total syntheses of bisbenzylisoquinoline alkaloids, evidently because commercial applications that could not be filled with isolated or semisynthetic materials have not developed, and because instrumental methods have made structure proof by interrelation of new alkaloids with known materials increasingly easy. 

The total synthesis of diphenyl ether-linked bisbenzylisoquinoline alkaloids must involve at some point the formation of the ether linkage(s). This pivotal... 

In order to circumvent the problem of low yields in the usual Ullmann reaction, most syntheses of bisbenzylisoquinoline alkaloids have formed the diphenyl ether linkages at an early stage and confronted the problem of isomer separation later. In the case of phaeantharine (18) (Section II,A,3), which has no asymmetric carbons, this approach was clearly preferred. This synthesis exemplifies the use of Reissert alkylation as a key step (9,269). Several analogs of bisbenzylisoquinoline alkaloids were prepared in an analogous manner (270,271). One... 

The synthesis of a number of bisbenzylisoquinoline alkaloids by direct dimerization of a phenolic benzylisoquinoline monomer is an extremely attractive... 

As a technique for partial synthesis, rearrangement of bisbenzylisoquinoline alkaloids has most often been used on spirodienones, as in the conversion of valdiberine to chitraline (Section n,C, 142), and is of value mainly in structure proof. 

O. N. Tolkachev, E. P. Nakova, and R. P. Evstigneeva, Usp. Khim. 49, 1617 (1980) (Chem. Abstr. 94, 15922). Synthesis of bisbenzylisoquinoline alkaloids. A general review in Russian, citing mainly older literature only five of 153 citations are more recent than 1969. 

T. Kametani, The Chemistry of the Isoquinoline Alkaloids, Vol. 2, Chapt. 7. Sendai Institute of Heterocyclic Chemistry, Sendai, 1974. A listing of 95 bisbenzylisoquinoline alkaloids arranged by structural types, with structures, molecular formulas, and references to papers citing physical properties, sources, structure proof, and synthesis. A comprehensive summary with 111 references. 

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 only bisbenzylisoquinoline alkaloids whose structures preclude the simple oxidative pairing mode of synthesis are those containing three diphenyl ether linkages (trilobine, isotrilobine, menisarine, normenis-arine, and micranthine). However, Barton and Cohen (10) have proposed a mechanism for the formation of the dibenzo-p-dioxin system of these alkaloids which comprises phenoxy free-radical coupling with a subsequent migration reaction. 

The following four new total syntheses of dimeric benzylisoquinoline alkaloids have been reported (—), (— )-00-dimethylcurine (288 R = Me),274 O-methyl-thalicberine (323 R = Me),275 ( )-0-methyltiliacorine (331),276 and ( )-obaberine (286 R1 = R2 = R3 = Me).277 The synthesis of O-methylthalic-berine, the first reported example of the bisbenzylisoquinoline alkaloids, is... 

Quinine and quinidine block potassium channels, both calcium independent ones and calcium-activated ones in several types of membranes [498,499, 500]. Quinine also has less specific effects on other ion channels — chloride as well as cations [501]. Blocking of potassium channels has a secondary effect of stimulating synthesis of phosphatidylserine and affecting other processes that are controlled by potassium concentration [289, 502, 503]. The bisbenzylisoquinoline alkaloid dauricine seems to act similarly to quinidine [504]. Some effects of quinine and quinidine, rather than showing actions on specific ion channels may come from more general effects on membrane structure. Quinidine does decrease the fluidity of liver plasma membrane [505] and it does interact with lipid bilayers [506]. 

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