There are many kinds of flavonoids which have interesting bioactivities in nature. Although many synthetic methods of the flavonoids have been developed, these methods are not always effective for highly substituted flavonoides. Herein we report more effective synthetic method for flavonoids through a β-diketone intermediate, which enabled us to synthesize six unnatural flavonoids (1a-c, 2a-c) and natural flavone C-glycosides, Chafuroside A (3) and B (4). The key intermediate 7 was easily synthesized by coupling of an acetophenone derivative 5 and N-acylbenzotriazole 6 under basic condition. Removal of TBDPS group with TBAF and subsequent cyclization under acidic condition gave a flavonoid 8. Finally, deprotection of benzyl groups furnished the flavone 1a in 5 steps. On the other hand, the flavonol 2a was also obtained by oxidation of 8 with DMDO and subsequent deprotection. (Scheme 1) Interestingly, flavones 1c and flavonol 2c exhibited potent sialyltransferase inhibitory activities. (Table 1) Chafuroside A (3) and B (4) are unique flavonoids isolated as minor constituent of oolong tea extract showed potent anti-inflammatory activity. Structurally, these flavones are consisting of unusual fused tetracyclic ring system composed of mannosyl moiety, A, and C rings of flavones framework. In order to synthesize 3 regioselectively, two hydroxyl groups of an aryl C-glycoside 9 were protected with TBDPS group and benzyl group, which afforded 13. The β-diketone 14 was synthesized by coupling between 13 and 6 followed by deprotection of TBDPS group. After cyclization of 14 under acidic condition, deprotection of Benzyl groups and intramolecular Mitsunobu reaction yielded 3. (Scheme 3) Thus, Chafuroside A (3) has been synthesized in 7 steps with 32% overall yield from 9. According to similar route, Chafuroside B (4) has been also synthesized in 5 steps and 13% yield from 9. (Scheme 4)
