gave the diastereomeric alkoxy ketones, 72α and 72β, in 28% and 12% yield, respectively.
Figure 2.27 Synthesis of cinnamtannin B1 based on the orthogonal activation approach.
Figure 2.28 Structure of (+)‐selligueain A, its monomeric flavan constituents, (+)‐afzelechin (AZ) and (–)‐epiafzelechin (EZ), and three monomeric synthetic units for orthogonal assembly.
Figure 2.29 Orthogonal activation and synthesis of selligueain A.
Figure 2.30 Synthesis of a series of dimeric PAs having A‐type structure via the Friedel–Crafts reaction.
The latter diastereomer 72β was subjected to condensation with nucleophilic flavan unit 52. Treatment of 72β with 52 in the presence of bentonite clay K‐10 gave the coupling products as a diastereomer mixture, which could be separated by silica gel column chromatography to give β‐adduct 73β and α‐adduct 73α in 52% and 7% yield, respectively. Subsequent two‐step deprotection, involving desilylation and hydrogenolysis of the benzyl ethers, allowed a spontaneous intramolecular acetal formation to give procyanidin A2 (3) in 80% overall yield from 73β and its bis‐2,4‐epi isomer 74 in 29% overall yield from 73α, respectively.
2.4 Conclusion
This chapter has reviewed an emerging class of oligomeric PAs possessing A‐type dual interflavan linkages, covering their structures, putative biosynthesis, and chemical synthesis. The research on this class of complex oligomers is still limited by the scarce availability of samples with high purity. For future progress, the role of organic synthesis is quite important, requiring the development of reliable synthetic methods, including (i) the flexible preparative methods of the flavan‐3‐ol monomeric constituents, and (2) facile means of constructing the [3.3.1]‐bicyclic skeleton with control of the stereo‐ and regiochemistry. The latter process needs to be reiterative, in dealing with the targets having multiple A‐type linkages. We hope this review will provide insights for further development and might serve as an invitation to researchers of various fields, attracting interest to this potentially exciting field.
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