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-->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-->2)-3,4-O-dibenzoyl-beta-L: -arabinopyranoside (2) from 4-methoxybenzoyl-beta-L: -arabinopyranoside 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-->2)-alpha-L: -arabinopyranoside (7), was selectively transformed to 4-methoxybenzoyl-2,3,4-tri-O-benzoyl-alpha-L: -rhamnopyranosyl-(1-->2)-4-O-acetyl-alpha-L: -arabinopyranoside (9) and 4-methoxybenzoyl-2,3,4-tri-O-benzoyl-alpha-L: -rhamnopyranosyl-(1-->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-->2)-alpha-L: -arabinopyranoside could be used as a nontoxic carrier moiety to enhance the activity of anticancer drugs.
Bang
Seong-Cheol
SC
College of Pharmacy, Chungnam National University, Daejeon, 305-764, Korea.
Seo
Hyun-Hee
HH
Shin
Hye-Rim
HR
Lee
Ki-Cheul
KC
Hoang
Le Tuan Anh
le TA
Jung
Sang-Hun
SH
D000840:Anisoles / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004187:Disaccharides / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D012503:Saponins / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry*
D000840:Anisoles; D000970:Antineoplastic Agents; D004187:Disaccharides; D012503:Saponins; D014315:Triterpenes; C010177:beta-hederin; D009828:Oleanolic Acid