An efficient synthesis of procyanidins. Rare earth metal Lewis acid catalyzed equimolar condensation of catechin and epicatechin

Syntheses of procyanidin B2 and B3 gallate derivatives using equimolar condensation mediated by Yb(OTf)3 and their antitumor activities

“…[2][3][4]22,23 Equimolar condensation between nucleophile 7 and electrophile 9 using Yb(OTf)3 as a Lewis acid to afford 11 in 53% yield. The benzylated procyanidin B2 3"-O-gallate (12) and procyanidin B2 3,3"-O-gallate (13) were also obtained from the condensation between nucleophile 8 and electrophile 10, nucleophile 8 and electrophile 9 in 22% and 43% yields, respectively.…”

“…The nucleophile 14, 15 and Similarly, related compounds of the procyanidin B3 the electrophile 16, 17 were prepared by the reported procedure. [2][3][4]22,23 Equimolar condensation between nucleophile 14 and electrophile 16 using Yb(OTf)3 as a Lewis acid to afford 18 in 68% yield. The benzylated procyanidin B2 3"-O-gallate (19) and procyanidin B2 3,3"-O-di-gallate (20) were also obtained from the condensation between nucleophile 15 and electrophile 17, nucleophile 15 and electrophile 16 in 28% and 68% yields, respectively.…”

“…As to the synthesis of 5, esterification between benzylated procyanidin B2 (22) and benzylated gallic acid (23) using DCC was effective. The antitumor activities of 1-6 suggested that these compounds showed significant cytotoxic activity but weaker than EGCG and prodelphinidin B3.…”

“…So far, we have developed an efficient synthesis of procyanidin dimers through equimolar condensation of catechin nucleophiles with electrophiles using Yb(OTf)3 as a Lewis acid. [22][23][24][25] Herein we demonstrate equimolar condensation of a catechin and/or a epicatechin nucleophile containing gallate moiety with a catechin and/or epicatechin derived electrophile and synthesis of procyanidin B2 and B3 gallates ( Figure 1). …”

Recent Syntheses of Proanthocyanidins

“…To overcome this problem, Makabe and co-workers investigated Lewis acid mediated equimolar condensation. 20,21 They chose tetrabenzylated catechin 17, as a nucleophilic unit, prepared by the Kawamoto's procedure 15 and electrophile unit 43 prepared by the Saito's method. 16 Equimolar condensation of 17 with 43 at room temperature was examined using various Lewis acids including rare earth metal at room temperature (Table 1).…”