(64g) Synthetic Study of Biofunctional Molecules by Using Microfluidic System

Recently, much effort has been devoted to the efficient and stereoselective synthesis of sialooligosaccharides in order to investigate their biological functions. We have developed an efficient α-sialylation by utilizing the highly reactive sialyl donor shaving C5-cyclic imides or azide, by virtue of the "fixed dipole effect"[1]. The scale-up in batch process, however, decreased the yield and selectivity, since the reaction control was difficult due to the high reactivity of the sialyl donor. The scale-up problem has now been circumvented by featuring the efficient mixing and fast heat transfer of the microfluidic system, providing the α-sialosides in excellent yields and selectivity[2]. Based on the established microfluidic sialylation and other microfluidic methods[3][4], our efforts on the solid-phase synthesis of N-glycan will also be presented. A saturated isoprene natural product, pristane, has been widely used as an adjuvant for antibody production. The availability from natural source is now very limited owing to the protection of several shark species. We have established a multi-kilogram synthesis of pristane, by applying the acid-mediated microfluidic dehydration of the allylic alcohol as the key step[5]. For the batch reaction, the diene product was partially decomposed during the prolonged reaction period, while the microfluidic reaction rapidly and cleanly gave the diene in excellent yield. The present protocol was generally useful for dehydration of β-hydroxyketone, simple alkanol, and allylic alcohols, giving corresponding olefins quantitatively. [1] Tanaka, K.; Goi, T.; Fukase, K. Synlett 2005, 2958-2962. [2] Tanaka, S.; Goi, T.; Tanaka, K.; Fukase, K. J. Carbohydr. Chem. in press. [3] Fukase, K.; Takashina, M.; Hori, Y.; Tanaka, D.; Tanaka, K. Kusumoto, S. Synlett 2005, 2342-2346. [4] Tanaka, K.; Fukase, K. Synlett 2007, 164-166. [5] Tanaka, K.; Motomatsu, S.; Koyama, K.; Tanaka, S.; Fukase, K. Org. Lett. 2007, 9, 299-302.