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

Abstract

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.

Chemical Strategies to Boost Cancer Vaccines

“…A flow chemistry system was applied in the fast synthesis of bisdesmosidic oleanolic acid saponins with C-28 and C-3 glycosylation based on continuous microfluidic and batch conditions. Only four steps with two purifications yielded different bisdesmosidic oleanolic acid saponins …”

“…Only four steps with two purifications yielded different bisdesmosidic oleanolic acid saponins. 241 Although CLRs recognize a large number of glycoside-based ligands, only a few receptors have been successfully developed for recognizing synthetic molecules. 156 For example, Kiessling and others successfully synthesized noncarbohydrate glycomimetics as DC-SIGN agonists.…”

Oleanolic Acid-3-(1′2′Orthoacetate-Glucoside)-28-Glucoside Alleviates Methylmercury Toxicity <i>in Vitro</i> and <i>in Vivo</i>

“…OA-3-(1′2′orthoacetate-Glu)-28-Glu was synthesized by deprotection of the C3-TES group in C28-acetylated glucoside as previously reported, 21) followed by preparation of orthoacetate under usual glycosylation condition with acetylated imidate donor, deprotection, and careful purification (Supplemental information).…”

Preparation of Tenuifolin from Polygala senega L. Root Using a Hydrolytic Continuous Flow System under High-Temperature, High-Pressure Conditions

“…Using this approach, the total time required for gram-scale preparation was shortened from 16 to 5 h in a continuous manner, and the yield was improved from 0.59% to 2.08% (w/w). Our group is continuing to apply this method in the quality control of Radix Polygalae and for the modification of tenuifolin for developing vaccine adjuvants.…”