Interflavanyl bond formation

Steynberg, P.J. et al.. Oligomeric flavanoids. Part 27. Interflavanyl bond formation in procyanidins under neutral conditions. Tetrahedron, 54, 8153, 1998. 

The biosynthesis of the proanthocyanidins is believed to proceed by addition of an electrophilic extension unit derived from a flavan-3,4-dioP or a flavan-3-oP to a nucleophilic starter unit, most likely a flavan-3-ol, with sequential addition of further chain-extension units. Although the genetics of interflavanyl bond formation in the proanthocyanidin polymerization process are not yet defmed, " the search for the elusive condensing enzyme continues unabated. ... 

One of the problems in procyanidin synthesis, is the lability of the interflavanyl bond under the very conditions for its formation. Such a labile interflavanyl bond invariably leads to an equilibrium between... 

The protocol depicted in Scheme 21, that is, initial formation of a heterodimeric ester of type (148), followed by TMSOTf-induced intramolecular formation of the (4 —> 8)-interflavanyl bond, and subsequent functional group manipulations, also permitted access to the phenolic octa-0-benzyl ethers of procyanidins B-1... 

Scheme 22 Formation of the interflavanyl bond of procyanidins under oxidative conditions.

It was anticipated that the C(4) benzylic ether bonds in proteraca-cinidins (39)-(42) would be susceptible to solvolysis in aqueous medium. The very same conditions which are applied universally for the formation of C(sp )—>C(sp ) interflavanyl linkages 40 would hence be less applicable to the generation of the ether bonds in compounds (39)-(42). We thus opted to enhance the electrophilicity at C(4) of one of the flavan-3,4-diol methyl ethers, e.g. (43) by formation of the 4-chloroflavan-3-ol derivative (44) in order to permit the formation of the crucial ether bond at near a neutral pH value. 

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