[The Journal of Organic Chemistry] Synthesis of bisdesmosidic oleanolic acid saponins via a glycosyl
We report the first synthesis of a series of bisdesmosidic oleanolic acid saponins using microflow reactor Comet X-01 via a continuous flow glycosylation-batch deprotection sequence. The main results of this study can be summarized as follows: (1) The microfluidic glycosylation of oleanolic acid at C-28 was achieved in quantitative yield and was applied to the synthesis of six C-28-monoglycosidic saponins. (2) The microfluidic glycosylation of oleanolic acid at C-3 was achieved in good yield without orthoester byproduct formation, and was applied to the synthesis of three bisdesmosidic saponins. (3) The continuous synthesis of saponins via a microfluidic glycosylation-batch deprotection sequence was achieved in four steps involving two purifications. Thus, the continuous microfluidic glycosylation-deprotection process is expected to be suitable for the preparation of a library of bisdesmosidic oleanolic acid saponins for in vivo pharmacological studies.
Naruki Konishi, Tatsuya Shirahata, Masaki Yokoyama, Tatsuya Katsumi, Yoshikazu Ito, Nozomu Hirata, Takashi Nishino, Kazuishi Makino, Noriko Sato, Takayuki Nagai, Hiroaki Kiyohara, Haruki Yamada, Eisuke Kaji, and Yoshinori Kobayashi J. Org. Chem., Just Accepted Manuscript DOI: 10.1021/acs.joc.7b00841 Publication Date (Web): May 31, 2017 Copyright © 2017 American Chemical Society