Synthesis of Bisdesmosidic Oleanolic Acid Saponins via a Glycosylation-Deprotection Sequence under Continuous Microfluidic/Batch Conditions

5 years ago

Synthesis of Bisdesmosidic Oleanolic Acid Saponins via a Glycosylation-Deprotection Sequence under Continuous Microfluidic/Batch Conditions

Tatsuya Katsumi, Tatsuya Shirahata, Hiroaki Kiyohara, Yoshinori Kobayashi, Takayuki Nagai, Kazuishi Makino, Eisuke Kaji, Naruki Konishi, Haruki Yamada, Nozomu Hirata, Masaki Yokoyama, Noriko Sato, Takashi Nishino, Yoshikazu Ito

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.

Publisher URL: http://dx.doi.org/10.1021/acs.joc.7b00841

DOI: 10.1021/acs.joc.7b00841