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

• Published in: Journal of organic chemistry Vol. 82; no. 13; pp. 6703 - 6719
• Main Authors: Konishi, Naruki, Shirahata, Tatsuya, Yokoyama, Masaki, Katsumi, Tatsuya, Ito, Yoshikazu, Hirata, Nozomu, Nishino, Takashi, Makino, Kazuishi, Sato, Noriko, Nagai, Takayuki, Kiyohara, Hiroaki, Yamada, Haruki, Kaji, Eisuke, Kobayashi, Yoshinori
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.07.2017; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ORGANIC-SYNTHESIS; NATURAL-PRODUCT; FACILE SYNTHESIS; ALPHA-SIALYLATION; CONTINUOUS-FLOW SYNTHESIS; FLASH CHEMISTRY; BOND FORMATION; CHEMICAL-SYNTHESIS; VACCINE ADJUVANTS; C-13 NMR DATA
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.7b00841

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.