Synthesis of naturally occurring noctyl PDglucopyranosides22

The Chinese natural medicine "Si Lie Hong Jing Tian" prepared from the underground part of R. (R.) quadrifida (PALL.) Fisch. et Mey. has been prescribed for hemostatic, antibechic and tonic purposes in Chinese traditional preparations and used as an endermic liniment for burns and contusions. Rhodiooctanoside (99) was isolated as one of the chemical constituents of R. quadrifida by M. Yoshikawa et al. and found to show potent histamine release inhibitory activity. The structure of 99 was determined to be octyl 6-O-a-L-arabinopyranosyl-P-D-glucopyranoside by spectroscopic analysis and chemical degradation studies. Meanwhile, n-octyl P-D-glucopyranoside (9) was isolated from the methanolic extract of the underground part of Rhodiola sachalinensis and is a non-ionic detergent which is effective for protein solubilization studies (Fig. 20). These ^-D-glucopyranosides were synthesized from n-octyl ^-D-glucopyranoside (9) or 8-hydroxyoctyl ^-d-glucopyranoside (27) as shown in Fig. 21.

i-glucopyranoside i-glucopyranoside

Figure 20: Structure of naturally occurring n-octyl ^-D-glucopyranosides.

Figure 20: Structure of naturally occurring n-octyl ^-D-glucopyranosides.

3.8.1. Synthesis of rhodiooctanoside (99)

As the yield of n-octyl P-D-glucopyranoside (9) by direct P-glucosidation was found to be low, conversion of 8-hydroxyoctyl P-D-glucopyranoside (27) to the desired P-glucoside (9) was carried out by means of chemoenzymatic method. Acetylation of 27 gave quantitatively a pentaacetate (100), which was treated with the lipase Amano P from Pseudomonas sp. to provide a mono-alcohol (101) in 80% yield along with the starting material (100). 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 101 with iodine (I2) in the presence of triphenylphosphine (Ph3P) gave quantitatively the corresponding iodide (102), which was subjected to reduction with NaBH4 to give a tetraacetate (103) in 92% yield. Finally, treatment of 103 with K2CO3 in MeOH provided the desired P-glucoside (9) in 89% yield. Consequently, overall yield (38% yield) of 9 from D-glucose via six steps is considerably improved in comparison to that (5.0-8.2% yield) by the direct P-glucosidation of 1-octanol. Tritylation of 9 gave trityl ether (104, 50% yield) along with the starting material (9, 50% recovery). Acetylation of 104 afforded quantitatively an acetate (105), which was subjected to hydrogenolysis in the presence of 20% Pd-C to provide a mixture (92% yield) of the desired 106 and 107 (106:107 = 3:1). Coupling reaction of this mixture and 2,3,4-tri-O-acetyl-a-L-arabinopyranosyl bromide in the presence of AgOTf and TMU gave the coupled product (108) in 50% yield. Finally, treatment of 108 with K2CO3 in MeOH provided quantitatively the synthetic rhodiooctanoside (99).

Was this article helpful?

0 0

Post a comment