Highly efficient and low-cost process for synthesis of 2-O-α-D-glucopyranosyl-6-O-(2-propylpentanoyl)-L-ascorbic acid

2-O-alpha-D-Glucopyranosyl-6-O-(2-propylpentanoyl)-L-ascorbic acid (6-bOcta-AA-2G) has shown a remarkable antitumor effect in an in vivo study. However, an efficient and low-cost process for synthesis of 6-bOcta-AA-2G has not been established yet. The process used for synthesis of 6-bOcta-AA-2G in this study consisted of three steps. The first step was acylation of L-ascorbic acid (AA) at the C-6 position with 2-propylpentanoic acid in concentrated H2SO4 at room temperature for 24 h to obtain 6-O-(2-propylpentanoyl)-L-ascorbic acid (6-bOctaAA). Next, specific glycosylation of 6-bOcta-AA at the C-2 position by cyclodextrin glucanotransferase (CGTase) from Thermoanaerobacter sp. was carried out using soluble starch as a low-cost glycosyl donor in acetate buffer (pH 6.0) at 40 degrees C for 24 h. In this glycosylation reaction by CGTase, oligoglucosylated 6-bOcta-AAs seemed to be generated, and thus these oligoglucosides were further hydrolyzed by amyloglucosidase from Rhizopus sp. at 40 degrees C for 1 h in the reaction mixture containing CGTase to efficiently obtain 6-bOcta-AA-2G. The overall yield of 6-bOcta-AA-2G was 19.4 %. The presented synthetic process can be used for mass production of 6-bOcta-AA-2G as an antitumor agent.

Automated summary

The study established an efficient and low-cost synthesis method for 6-bOcta-AA-2G, involving acylation, specific glycosylation by CGTase, and further hydrolysis by amyloglucosidase. The overall yield of 6-bOcta-AA-2G reached 19.4%, demonstrating a potential for mass production as an antitumor agent.