Synthesis of naturally occurring benzyl PDglucopyranoside

Prunus mume Sieb. et Zucc. (Rosaceae) has been used as medicinal food in Japan for a long time and is reported to have many pharmacological properties, such as inhibitory effects on bradykinin and prostaglandin E2 production in the abdominal cavities of mice and the effects on angiotensin-converting enzyme, aldosterone and corticosterone levels in rat plasma. Moreover, it has been reported that the methanolic extract of P. mume exhibited inhibitory effects on rat lens aldose reductose and platelet aggregation. Benzyl ^-D-glucopyranoside (1) is one of the pharmacologically active constituents of P. mume. On the other hand, three kinds of naturally occurring benzyl 6-O-glycosyl-^-D-glucopyranoside congeners, benzyl 6-O-^-D-xylopyranosyl-P-D-glucopyranoside (54), benzyl 6-O-a-L-rhamnopyranosyl-^-D-glucopyranoside (55) and benzyl 6-O-a-L-arabinopyranosyl-^-D-glucopyranoside (56) were isolated from Alangium chínense, Margyricarpus setosus and Lycopersicon esculentum, respectively (Fig. 9).

Benzyl p-D-glucapyranoside (1) R1 = H Benzyl 6-O-p-d-xylopyranosyl-p-D-glucopyranoside (54) „1 =

Benzyl 6-O-a-L-rhamnopyranosyl-p-D-glucopyranoside (55)

Benzyl p-D-glucapyranoside (1) R1 = H Benzyl 6-O-p-d-xylopyranosyl-p-D-glucopyranoside (54) „1 =

Benzyl 6-O-a-L-rhamnopyranosyl-p-D-glucopyranoside (55)

Benzyl 6-O-a-L-arabinopyranosyl-p-D-glucopyranoside (56) OH

Benzyl 6-O-a-L-arabinopyranosyl-p-D-glucopyranoside (56) OH

Figure 9: Structure of naturally occurring benzyl ^-D-glucopyranosides.

These ^-D-glucopyranosides were synthesized from benzyl ^-D-glucopyranoside (1) as shown in Fig. 10.

3.3.1. Synthesis of benzyl 6-O-P-D-xylopyranosyl-P-D-glucopyranoside (54) Silylation of 1 gave a silyl ether (57, 95% yield), which was subjected to acetylation to afford an acetate (58) in 99% yield. Deprotection of the silyl group of 58 using 1 M IBr solution in CH2Cl2 gave a primary alcohol (59) in 76% yield. When 2% I2 in MeOH solution or N-bromosuccinimide (NBS) instead of 1 M IBr solution in CH2Cl2 was applied for desilylation of 58, the yield of 59 was improved to 90 or 98%, respectively. By the following reported procedure, the coupling reaction of benzyl ^-D-glucopyranoside congener (59) and phenyl 2,3,4-tri-O-acetyl-1-thio-^-D-xylopyranoside in the presence of N-iodosuccinimide (NIS) and trifluoromethanesulfonic acid (TfOH) gave a mixture (60:61 = 3 : 2) of the coupled products 60 and 61 in 40% yield. Finally, treatment of this mixture with K2CO3 in MeOH provided the synthetic benzyl 6-O-^-D-xylopyranosyl-P-D-glucopyranoside (54, 55% yield) and benzyl 6-O-^-D-xylopyranosyl-P-D-glucopyranoside (62, 37% yield). Whereas, 61 was formed by glycosylation of benzyl 2,3,6-tri-O-acetyl-^-D-glycopyranoside (59a), which was formed from 59 by 4 ^ 6 acyl migration in the reaction medium.

3.3.2. Synthesis of benzyl 6-O-a-L-rhamnopyranosyl-fi-D-glucopyranoside (55)

Ethyl 2,3,4-tri-O-acetyl-1-thio-a-L-rhamnopyranoside was synthesized by applying the reported method based on the BF3 -Et2O-catalyzed reaction of ethane

thiol and tetra-O-acetyl-a-L-rhamnopyranoside obtained by acetylation of a-L-rhamnose. By the following reported procedure, the coupling reaction of benzyl P-D-glucopyranoside congener (59) and ethyl 2,3,4-tri-O-acetyl-1-thio-a-L-rhamnopyranoside in the presence of N-iodosuccinimide (NIS) and trifluoromethanesulfonic acid (TfOH) gave the coupled product (63) in 76% yield. Finally, treatment of 63 with K2CO3 in MeOH provided the synthetic benzyl 6-O-P-D-rhamnopyranosyl-P-D-glucopyranoside (55) in 85% yield.

3.3.3. Synthesis of benzyl 6-O-a-L-arabinopyranosyl-fi-D-glucopyranoside (56)

By following the reported procedure, the coupling reaction of benzyl P-D-glucopyranoside congener (59) and 2,3,4-tri-O-acetyl-a-L-arabinopyranosyl bromide in the presence of silver triflate (AgOTf) and 4A molecular sieves gave the coupled product (64) in 40% yield. Finally, treatment of 64 with K2CO3 in MeOH provided quantitatively the synthetic benzyl 6-O-a-L-arabinopyranosyl-P-D-glucopyranoside (56).

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