2016 Volume 74 Issue 5 Pages 412-425
Summarized in this article are the syntheses of food effective constituents catechin and flavone toward the development for chemical biology investigations. Synthesis of (-)-5,7-dideoxy-gallocatechin (21a) was accomplished by 6-endo cyclization of corresponding epoxy-phenol 18. Inspired by the finding that (-)-5,7-dideoxy-epigallocatechin gallate (21b) possessed same biological activity with natural epigallocatechin gallate (1), we designed APDOEGCg (40) as a useful probe precursor. Synthesis of APDOEGCg (40) was accomplished by cationic cyclization utilizing neighboring participation of the gallate carbonyl group. Furthermore, the synthetic APDOEGCg (40) was readily converted to fluorescein probe 42 and immunogen 45 efficiently due to its high reactivity of amine functional group. The synthetic probes were demonstrated the imaging studies and the generation of antibodies. Regioselective synthesis of methylated-EGCgs 46 and 47 was accomplished by employment with the 2-nitrobenzenesulfonyl (Ns) as a novel protecting group of phenols. Additionally utilizing the synthetic 4,4"-diMe-EGCg (54) as an authentic sample, a rapid synthesis of PET probe 55 by incorporation of 11C atom into the EGCg derivative 47 was demonstrated efficiently. Biomimetic synthesis of theaflavin (56) from catechins (3 and 59) was also accomplished by using Ns protecting group to minimize undesired side reactions of electron-rich aromatic rings. Regioselective synthesis of chafurosides A and B (70 and 71) were accomplished from the same intermediate (78a). The both flavone rings were constructed from β-diketone intermediate (72), which was readily obtained by condensation of an acyl donor (79) and ketone (78c). Utilizing our novel flavone synthetic method, practical synthesis of nobiletin (88), a polymethoxylated flavone from citrus, was accomplished in hundred gram-scale. Synthetic nobiletin was readily converted to PET prove (99) by selective demethylation and rapid incorporation of 11C atom.