Study On The Methodologies Of Regioselective Conversion Of The O-TMS And O-Benzyl Protecting Group In The Synthesis Of Carbohydrates

Carbohydrates and glycoconjuagates are important matters of life and play a key role in signal transduction and biorecognition in cells. As carbohydrates are very complex and heterogeneous, it is difficult to obtain carbohydrates with high purity by isolating from nature. Thus chemical synthesis is of great significance for glycochemistry research and commercial applications. However, due to the numerous hydroxyl groups in carbohydrates, it is a challenge for the chemical synthesis of carbohydrates. Regioselective protection-deprotection strategy is an effective solution. In this thesis, we studied on the methodologies of regioselective conversion of the O-TMS and O-Benzyl protecting group in the synthesis of carbohydrates. The results are follows:(1) Per-O-trimethylsilylated D-lactose1a was treated with ammonium acetate in the co-solvent of CH2C12and CH3OH (v/v=1/1) at r.t. to afford C-6mono-detrimethylsilylated lactose2a in good yield. This methodology was extended to per-O-trimethylsilylated cellobiose and trehalose successfully. It has several advantages such as mild reaction conditions and high regioselectivity. Then the mono-detrimethylsilyated D-lactose2a underwent azidation and acetylation at C-6free hydroxyl group respectively. Therefore, an economic and eco-friendly strategy for the asymmetric modification of disaccharides was achieved;(2) Per-O-trimethylsilylated α-cycodextrin was treated with acetic anhydride in the presence of acetic acid in pyridine. The TMS groups on the primary face of CD were converted into acetyl groups directly. This methodology has several advantages as follows:the starting material per-O-trimethylsilylated CDs were easily prepared; it was an one-pot conversion which simplified synthetic procedures; the obtained acetylated CD product6a could be detrimethylsilylated rapidly in the40%actetic acid aqueous solution to afford a useful CD intermediate7a for the modification on the secondary face of CD.(3) The possibility of regioselective acrylation of per-O-benzyl protected a-cycodextrin in the presence of different Lewis acid was studied. And we developed an efficient methodology involving direct conversion of benyl groups on the primary rim of cyclodextrin to the corresponding acryl groups in the presence of acrylic anhydride with BF3-Me2O catalyst. Compared to the methods reported, it has advantages of less procedures and more mild conditions. Meanwhile, the products obtained can be valuable precursors for the thiol-ene click reaction or other further modification of carbohydrates.This methodology was applied successfully in6-O-acryl regioselective introduction from benzyl2,3,4,6-tetra-O-benzyl-β-mannopyranoside as well.