Studies On The Synthesis Of Salidroside

Salidroside is one of the effective componests of Rhodiola rosea extract. It has exhibited anti-virus, anti-tumor, anti-aging, anti-radiation properties, and can improve immune system, protect cardiovascular system and central nerve system. The Rhodiola rosea is the alpine perennial herb with decreasing reservation. The low content in Rhodiola rosea extract and low yeild of purification makes the cost high. Chemical synthesis is a fast and very efficent way to meet the needs. At present, the reported chemical synthesis methods suffered with low yield and high cost. Based on the previous works, some routes were designed to optimize the synthesis in this paper.(1) The glycoside donor2,3,4,6-O-tetra-acetyl-α-D-glucopyranosyl trichloroacetimidate was synthesised by multi-step reactions of acetylation, de-1-O-acetyl and1-O-trichloroacetimidate, with the D-glucose as the starting material. Triflate trimethylsilyl ester (TMSOTf) was used as catalyst in the glycosylation. The coupling condition between donor and unprotected4-(hydroxy)phenethyl alcohol were studyied. The low yield (15.6%) and difficulty of purificaiton make this method unsuitable for massive synthesis.(2) To reduce the difficulty of the separation of salidroside using2,3,4,6-O-tetra-acetyl-α-D-pyran glucose trichloroacetimidate as donor and improve the yield of the glycosylation reaction,2,3.4,6-O-4-benzoyl -a-D-pyran glucose trichloroacetimidate was used as glycosylation donor to synthesize the salidroside, reacted with4-(hydroxy)phenethyl alcohol. The results showed that the glycosylation reaction yield was slightly improved (21.5%) compared to2,3,4,6-0-tetra-acetyl-α-D-pyran glucose trichloroacetimidate glycosylation donor, and a significant reduction difficult of separation and purification in the target product.(3) To improve the glycosylation reaction yield, the glycoside donor2,3,4,6-O-tetra-benzyl-α-D-pyran glucose trichloroacetimidate protected by electron-donating group was used as glycosylation donor. TMSOTf was used as catalyst in the glycosylation of donor and receptor4-(benzyloxy)phenethyl alcohol. The yields had been greatly improved (82.6%), but its stereoselectivity (α:β=53:47) was low, because of lacking of2-O-acyl neighbouring group participation, which increased the difficulty of separation and purification.(4) The glycosylation donor1-bromo-2,3,4,6-tetra-O-acetyl-α-D-pyran glucose was synthesized by reactions of acetylation and1-O-bromination with the D-glucose as the starting material. Ag2O was used as catalyst in the glycosylation of glycosylation donor and glycosylation receptor4-(benzyloxy)phenethyl alcohol. The yield of the glycosylation reaction was higher (73.5%) and stereoselectivity (100%). However, the catalyst was used in higher price. If the mass production of salidroside, the AgBr should be to recovered to reduce production costs. The four synthetic routes discussed in this article had been successfully accomplished. There were some advantages and disadvantages in the four routes. The yields were low with2,3,4,6-O-tetra-acetyl-α-D-pyran glucose trichloroacetimidate and2,3,4,6-O-4-benzoyl-α-D-pyran glucose trichloroacetimidate as glycosylation donor and the yield was high with2,3,4,6-O-tetra-benzyl-α-D-pyran glucose trichloroacetimidate as glycosylation donor whose stereoselectivity was low. High yield and stereoselectivity can be got by using1-bromo-2,3,4,6-tetra-β-acetyl-α-D-pyran glucose as glycosylation donor, while the economic cost is high. Combined with the advantages and disadvantages of various synthetic routes, four synthetic routes should be further optimized. Through these findings of this article, salidroside could be further developed and utilized in the future.