Synthesis of Ring A-Modified Baicalein Derivatives

Baicalein, an important active constituent of the traditional Chinese herb Scutellaria baicalensis, exhibited antitumor activity and inhibitory activity against P-gp 170. The syntheses of 25 baicalein derivatives, 226 (Table), are described here (Scheme 1). These compounds were systematically modified with O-alkylation and O-acylation at HO?C(5), HO?C(6), and HO?C(7), singly or in combination, on the ring A of baicalein in order to evaluate the effects of such modifications on their inhibitory activities against multidrug-resistant tumor cell lines and P-gp 170. Highly selective and efficient alkylations at HO?C(7) of peracetylated baicalein were the key to the distinction between HO?C(6) and HO?C(7) of baicalein.