Synthesis Of A Series Of Alkyl Dimer (1â†'6) -2-amino-2-deoxy-β-d-glucopyranosides

Transdermal drug delivery system is a hot-pot in the pharmaceutical researches in recent years. However, the delivery flux and efficiency of most drugs permeating through skin are very slow because of the skin barrier. So serious attentions are put on seeking effective penetration enhancers in the field of transdermal drug delivery. Amino-oligosaccharide supplies advantages for the research of effective and safe transdermal enhancers for its excellent biocompatibility and particular biological activity. This dissertation was focused on the synthesis of series of alkyl dimer (1→6)-2-amino-2-deo-xy-β-D-Glucopyranosides from the starting material D-glucos- amine in order to study biomimic glyco-based transdermal enhancers.Firstly,the amine in D-glucosamine was first protected by phthalimido,then the hydroxy groups were acetylated to obtain the important intermediate 1,3,4,6-tetra-O-acetyl- 2-phthalimido-2-deoxy-β-D-glucopyranoside. The acetyl of this intermediate was removed selectively with weak base, then reacted with trichloroacetonitrile in the presence of DBU to give the sugar donor , 3,4,6-tri-O- acetyl-2-phthalimido-2-deoxy-β-D-Glucopyranoside trichloroacetimidate ester.Next, the alkyl chain was introduced, in the presence of SnCl₄, to the C-1 of the intermediate 1,3,4,6-te tra-O-acetyl-2-phthalimido-2-deoxy-β-D-glucopyranoside, which was then de-O-acetylated with sodium methoxide. Afterwords, TrCl was devoted to selective protection of 6-hyroxy while acetyl groups were used to protect other hydroxyl groups. In the end, trityl was removed selectively with 80% acetic acid to produce a series of glucoreceptor alkyl-3,4-di-O-acetyl-2-deoxy-2- phthalimido-β-D-glucopyranoside.Afterwards, glucoreceptors were allowed to react with the sugar donor under the action of TMSOTf to get a series of disaccharides, of which the acetyl groups were removed with sodium methoxide and the amino phthaloyl protective group was removed with NH₂NH₂. Structures of the obtained products, alkyl dimer (1→6)-2- amino-2-deoxy-β-D-glucopyranosides, were confirmed by IR,1HNMR and ESI-MS.Finally, this dissertation summarized the isomerisms during the synthesis process and the isomers were charaterized. The isomerization mechanism was discussed to lay the foundation for subsequent synthesis.