Total synthesis of apigenin 7,4′-di-O-β-glucopyranoside, a component of blue flower pigment of Salvia patens, and seven chiral analogues

We have succeeded in the first total synthesis of apigenin 7,4′-di-O-β-d-glucopyranoside (), a component of blue pigment, protodelphin, from naringenin (). Glycosylation of according to Koenigs–Knorr reaction provided a monoglucoside in 80% yield, and this was followed by DDQ oxidation to give apigenin 7-O-glucoside (). Further glycosylation of 4′-OH of with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl fluoride () was achieved using a Lewis acid-and-base promotion system (BF3·Et2O, 2,6-di-tert-butyl-4-methylpyridine, and 1,1,3,3-tetramethylguanidine) in 70% yield, and subsequent deprotection produced . Synthesis of three other chiral isomers of , with replacement of d-glucose at 7 and/or 4′-OH by l-glucose (), and four chiral isomers of apigenin 7-O-β-glucosides () and 4′-O-β-glucosides () also proved possible.