A Convenient Preparation of a Disaccharide Motif and its Role in the Cytotoxicity of the Triterpenoid Saponin, $\alpha$-Hederin

The sugar structures of triterpenoid saponins, such as $\alpha$-hederin, are intimately associated with their antitumor activities and other biological activities. The $\alpha$-L-rhamnopyranosyl-($1{\rightarrow}2$)-$\alpha$-L-arabinopyranoside group of $\alpha$-hederin alters the cytotoxicity of its aglycon, hederagenin. This study explored the role of this saccharide unit in the cytotoxic effect of $\alpha$-hederin and the possibility of its use as a carrier moiety in prodrugs of anticancer agents. A new convenient and practical procedure for the preparation of 4-methoxybenzoyl-2,3,4-tri-O-benzoyl-$\alpha$-L-rhamnopyranosyl-($1{\rightarrow}2$)-3,4-O-dibenzoyl-$\beta$-L-arabinopyranoside (2) from 4-methoxybenzoyl-$\beta$-Larabinopyranoside was accomplished using four steps with an overall yield of 63%. The use of $BF_3-OEt_2$ as a catalyst in the glycosylation step in this procedure had a large advantage over the TMSOTf catalyst used in the usual method. Moreover, the key intermediate obtained in this procedure, 4-methoxybenzoyl-2,3,4-tri-O-benzoyl-$\alpha$-L-rhamnopyranosyl-($1{\rightarrow}2$)-$\alpha$-L-arabinopyranoside (7), was selectively transformed to 4-methoxybenzoyl-2,3,4-tri-O-benzoyl-$\alpha$-L-rhamnopyranosyl-($1{\rightarrow}2$)-4-O-acetyl-$\alpha$-L-arabinopyranoside (9) and 4-methoxybenzoyl-2,3,4-tri-Obenzoyl-$\alpha$-L-rhamnopyranosyl-($1{\rightarrow}2$)-3-O-benzoyl-$\beta$-L-arabinopyranoside (10). These derivatives did not show any cytotoxicity against human cancer cell lines. Thus the 3-O-$\alpha$-L-rhamnopyranosyl-($1{\rightarrow}2$)-$\alpha$-L-arabinopyranoside could be used as a nontoxic carrier moiety to enhance the activity of anticancer drugs.