@article{f25f1cb13fea4e8aaf800482ac9a2abc,
title = "Synthesis and tumor cytotoxicity of novel N-substituted glucosamine-bearing oleanolic acid derivatives",
abstract = "Eleven novel triterpenoid saponins, N-substituted-β-D-glucosaminide derivatives of oleanolic acid, were designed and synthesized via a stepwise glycosylation strategy. These compounds were evaluated for in vitro cytotoxic activity against six different tumor cell lines. Most of the compounds inhibited the growth of, at least, one tumor cell line effectively at micromolar concentrations. Preliminary structure-activity relationships(SARs) indicate that acylation of the nitrogen of the glucosamine-bearing triterpenoid saponins affords the compounds that are highly cytotoxic towards specific tumor cell lines.",
author = "Li Ren and Yang Liu and Guihua Yu and Yuan Gao and Xin Liu and Bo Wang and Xiaonan Deng and Maosheng Cheng",
note = "Funding Information: We previously designed and synthesized three series of diosgenyl glucosaminides containing cinnamoyl, carbamido and thiosemicarbazone substituents at their amino groups to investigate their in vitro cytotoxicity. Preliminary in vitro screening indicates that some saponins from the cinnamoyl series show moderate to excellent antiproliferative activity against cell lines, and this series is more active than the other series[10]. Inspired by this result, we have found that the introduction of trans-cinnamic acid onto other glucosamine saponins resulted in more potent lead compounds. Therefore, we attempted to investigate the possibility that oleanolic acid, the Based on our experiences with triterpenoid saponin synthesis[11―14], a stepwise glycosylation strategy was adopted for the synthesis of novel derivatives, as this strategy generally affords the 1,2-trans-glycosidic linkage exclusively. The 2,2,2-trichloroethoxycarbonyl group(Troc) was used to protect the amino group in peracetylated glucosaminide trichloroacetimidate(SD-1) in order to avoid the formation of oxazoline derivatives during the glycosylation process[12,15]. The synthetic route began with the glycosylation reaction between the benzyl ester of oleanolic acid(1)[11] and SD-1 catalyzed by trimethylsilyl trifluoromethanesulfonate(TMSOTf) in a well-established procedure(Scheme 1)[16,17]. The glycosidic bond of intermediate 2 was in the β orientation(demonstrated by the 8.1 Hz coupling constant of J1-2 in 1H NMR) due to neighboring group participation of the Troc moiety. The Troc group was removed by treatment with Zn and AcOH to afford compound 3. Substituted cinnamoyl chlorides were prepared via Knoevenagel reactions between commercially available substituted benzaldehydes and malonic acid. These cinnamoyl chlorides were condensed with amine 3 in the presence of pyridine to afford intermediates 4a―4k. Finally, the removal of the benzyl group through catalytic hydrogenation and global deacetylation with NH3-MeOH ——————————— *Corresponding authors. E-mail: mscheng@syphu.edu.cn; y.liu@syphu.edu.cn Received November 27, 2013; accepted April 28, 2014. Supported by the National Natural Science Foundation of China(Nos.21142010, 81273358) and the PhD Scientific Research Opening Foundation Projects of Liaoning Province of China(No.20091081). {\textcopyright} Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH representative aglycone of triterpenoid saponins, might exhibit similar properties. The present work describes initial studies on the synthesis of eleven novel N-substituted glucosamine-bearing oleanolic acid derivatives and the evaluation of their cytotoxic activity against tumors.",
year = "2014",
month = aug,
doi = "10.1007/s40242-014-3522-3",
language = "English (US)",
volume = "30",
pages = "639--643",
journal = "Chemical Research in Chinese Universities",
issn = "1005-9040",
publisher = "Jilin University Press",
number = "4",
}