Sumei Ren

Structure-activity relationships of saponin derivatives: a series of entry inhibitors for highly pathogenic H5N1 influenza virus.

The occurrence of highly pathogenic avian influenza virus H5N1 highlights the urgent need for new classes of antiviral drugs. Theoretically, each of steps in influenza viral life cycle can be a target of antiviral therapeutics. However, up to date, no licenced entry inhibitor drug is available for H5N1 or any other influenza viruses. Our strategy for developing new anti-influenza therapeutics is to target the interaction between HA and sialic acid which is influenza viral receptor presented on host cell surface. Here, based on our previously discovered small molecule inhibitor saponin 1, intensive SAR studies around the sugar chain and aglycone were conducted. The results showed that both the chacotriosyl residue and the chlorogenin moiety of active compound 1 are important for the antiviral activity, although several subtle modifications can be made on particular positions.

Synthesis and Biological Evaluation of Analogs of Methyl Ursolate 3-O-β-Chacotrioside as H5N1 Viral Entry Inhibitors

The earliest stage of influenza virus infection is the viral entry to the host cell. In our previous work, we discovered the first three small molecule H5N1 viral entry inhibitors 1–3. Here, based on saponin 3, methyl ursolate 3-O-β-chacotrioside, several analogs were synthesized and evaluated to understand the structure-activity relationships of this type of compound on the H5N1 viral entry inhibitory activity. The preliminary studies demonstrated that unlike saponins 1 and 2, it is possible to reduce the 3-O-chacotriosyl residue of compound 3 to a disaccharide without affecting the viral entry activities significantly. The results obtained will render new clues to the understanding of the antiviral profile for these types of compounds.

Glycosylation of a Ketone with an O-Glycosyl Trichloroacetimidate Provides an Enol Glycoside

An enol-type glycosylation reaction has been investigated. Enol glycosides can be obtained from the reaction between O-glycosyl trichloroacetimidates and the corresponding ketones promoted by an acid. The enol glycosides derived from cyclic ketones can be afforded efficiently and isolated in good yield, while those from acyclic ketones are prepared in low conversion or are too labile for isolation. Further studies on different glycosyl donor types indicate that only the O-glycosyl trichloroacetimidate works well as a donor for enol glycosylation.

Concise total synthesis of acylated phenolic glycosides vitexnegheteroin A and ovatoside D

Starting from readily available vanillin and α-D-acetobromo glucose, two natural acylated phenolic glycosides vitexnegheteroin A and ovatoside D were synthesized for the first time in 4 steps with overall yields of 54% and 65%, respectively. The key steps involve the directly regioselective O-6 acylation of vanillin β-D-glucopyranoside with acyl chlorides, and simultaneous removal of the allyl protecting groups on the phenolic acid moiety and reduction of the aldehyde in the aglycon moiety by using Pd(PPh)3-NaBH4 system in one pot.