The Study On Synthesis And Biological Activities Of Methyl 6-deoxyl-6-guanidinoglucosides

Many guanidines isolated from natural products or artificially synthesized show significant antitumor, antiviral, and antifungal activities. Some guanidines bearing thiazolyl and glycosyl moiety are reported to serve as HIV-1 protease, HIV-1 reverse transcriptase inhibitors, angiotensin converting enzyme inhibitors (ACEI), and nitric oxide synthase (NOS) inhibitors. In order to broaden the synthesis and bioactivity research of guanidinoglycosides, we used peracetylated methyl 6-deoxy-6-isothiocyanato-D-glucopyranoside as the starting material to synthesize a series of new methyl 6-deoxy-6-guanidinoglucoside compounds. A novel protocol for synthesizing guanidinoglucoside was investigated. The structures of all the synthesized compounds were confirmed by analytical analysis, spectral data (IR, NMR and MS) and X-ray single crystal diffraction. Some of these guanidine derivatives showed potential bioactivity against influenza virus.The major accomplishments of this treatise:1. Using anhydrous D-glucose as the starting material, methyl 2,3,4-tri-O-acetyl-6-deoxy-6- isothiocyanato-α-D-glucopyranoside was synthesized by methyl glycosidation, tosylation of 6-OH, azide substitution, acetylation, and then Staudinger-Aza-Wittig reaction with PPh3-CS2 under argon gas atmosphere, which reacted with 2-amino-benzothiazole derivatives in dry pyridine to give sugar-thioureas. Treatment of sugar-thioureas with various amines and using HgCl2 or HgO as a regent of desulfurization gave series of methyl 2,3,4-tri-O-acetyl-6-deoxyl-6-guanidino-α-D-glucopyranosides.2. Methyl 2,3,4-tri-O-acetyl-6-deoxyl-6-guanidino-α-D-glucopyranosides were deacetylated in MeOH/NaOMe to give series of methyl 6-deoxyl-6-guanidino-α-D-glucopyranosides.3. In the course of the guanidinylation, the desulfurizing effect of several kinds of heavy metal compounds was investigated. HgO-MS 4? was found to be an efficient reaction reagent in synthesis guanidines bearing thiazolyl and glycosyl moiety.4. The bioactivities of some representative compounds were investigated.The major innovations of this treatise:1. The full route of synthesizing methyl 2,3,4-tri-O-acetyl-6-deoxy-6-isothiocyanato-α- D-glucopyranoside was defined by using anhydrous D-glucose as the starting material.2. Using dry pyridine as the solvent, the protocol of non-anomeric glycosyl isothiocyanate reacting with low-reactive aryl amines was defined.3. A novel class of trisubstituted guanidinoglucosides were obtained under mild conditions and with high yields when utilizing Hg(II) as desulfurizing agents. All compounds haven't been reported in the literatures.4. The HgO-MS 4? protocol is a more effective and convenient method in the reaction of sugar thioureas with amines than the HgCl2-Et3N-DMF method.