Synthesis of naturally occurring hexyl PDglucopyranosides23

n-Hexyl P-D-glucopyranoide (7) was isolated as one of the chemical constituents of R. quadrifida by M. Yoshikawa et al. and reported to increase blood pressure. Meanwhile, n-hexyl 6-O-P-D-xylopyranosyl-P-D-glucopyranoside (109) was isolated from the dried roots of Rehmannia glutinosa Libosh. var. purpurea Makino. These P-D-glucopyranosides were synthesized from n-hexyl P-D-glucopyranoside (7) or 6-hydroxyhexyl P-D-glucopyranoside (25) as shown in Figs 22 and 23.

n-Hexyl 6-O-p-D-xylopyranosyl-fS-D-glucopyranoside (109) R1 = H n-Hexyl p-D-glucopyranoside (7)

Figure 23: Synthesis of naturally occurring n-hexyl ^-D-glucopyranosides.

Figure 23: Synthesis of naturally occurring n-hexyl ^-D-glucopyranosides.

3.9.1. Synthesis of n-hexyl fi-D-glucopyranoside (7) and n-hexyl 6-O-f-D-xylopyranosyl-f-D-glucopyranoside (109)

As the yield of n-hexyl ^-D-glucopyranoside (7) by direct ^-glucosidation was found to be low, conversion of 6-hydroxyhexyl ^-D-glucopyranoside 25 to the desired ^-glucoside (7) was carried out by means of chemoenzymatic method. Acetylation of 25 gave quantitatively a pentaacetate (110), which was treated with the lipase Amano P from Pseudomonas sp. to provide a mono-alcohol (111) in 80% yield along with the starting material (110). In this enzymatic hydrolysis, the terminal acetyl group in the side chain was selectively hydrolyzed and other acetyl groups in the sugar part were found to be intact. Treatment of 111 with iodine (I2) in the presence of Ph3P gave quantitatively the corresponding iodide (112), which was subjected to reduction with NaBH4 to give a tetraacetate

(113) in 88% yield. Finally, treatment of 113 with K2CO3 in MeOH provided the desired P-glucoside (7) in 87% yield. Consequently, overall yield (41.6% yield) of 7 from D-glucose via six steps is considerably improved in comparison to that (8.8-13.5% yield) by the direct P-glucosidation of 1-hexanol. Tritylation of 7 gave a trityl ether (114, 79% yield) along with the starting material (7, 20% recovery). Benzoylation of 114 afforded a benzoate (115) in 97% yield, which was subjected to hydrogenolysis in the presence of 20% Pd(OH)2-C to provide the desired 116 in 97% yield. On the other hand, methylthio 2,3,4-tri-O-acetyl-P-D-xylopyranoside was synthesized by applying the reported method based on the reaction of (methylthio)trimethylsilane and tetra-O-acetyl-P-D-xylopyranoside obtained by acetylation of D-xylose. By applying the reported procedure, coupling reaction of n-hexyl P-D-glucopyranoside congener (116) and methylthio 2,3,4-tri-O-acetyl-P-D-xylopyranoside in the presence of AgOTf and PhSeCl gave the coupled product (117) in 69% yield. Finally, treatment of 117 with K2CO3 in MeOH provided quantitatively the synthetic n-hexyl 6-O-P-D-xylopyranosyl-P-D-glucopyranoside (109).

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