doiSerbia

Improved synthesis of gastrodin, a bioactive component of a traditional Chinese medicine

Li Yu-Wen (Qingdao Agricultural University, School of Chemistry and Pharmacy, Qingdao, China)
Ma Cui-Li (Qingdao Agricultural University, Affiliated Hospital, Qingdao, China)

Highly practical synthesis of gastrodin has been developed using penta-O-acetyl-b-D-glucopyranose and p-cresol as glycosyl donor and glycosyl acceptor, respectively, in four steps with 58.1% overall yield. At the initial step, the penta-O-acetyl-b-D-glucopyranose was treated with p-cresol in the presence of BF3.Et2O as catalyst to generate 4-methylphenyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside in 76.3% yield. Furthermore, this product was subjected to radical bromination with NBS to provide 4-(bromomethyl) phenyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside in 91% yield. Subsequently, reaction of 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside with a solution of acetone and saturated aqueous sodium bicarbonate led to 4-(hydroxylmethyl) phenyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside in 93% yield. Finally, global deprotection of 4-(hydroxylmethyl) phenyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside under Zemplen conditions furnished gastrodin in 90% yield. Compared to the previously reported methods, this protocol has advantages of operational simplicity, chromatography-free separation, high overall yield, inexpensive and common reagents as well as less waste pollutants, rendering it an alternative suitable for industrial production.

Keywords: gastrodin, glycosylation, penta-O-acetyl-b-D-glucopyranose, radical bromination