Studies On The Stereoselective Synthesis Of 2,6-Dideoxy Glycosides And 5-Aza Angucycline Analogues

This thesis was composed of three parts:1.Research on the synthesis of alkyl 2,6-dideoxy-O-glycosides;2.Stereoselective synthesis of ?-aryl 2,6-dideoxy-O-glycosides;3.Research on the synthesis of 5-aza angucycline analogues.1.2,6-Dideoxy sugars are common units in many natural products and clinical reagents.The sugar moiety of these compounds has shown important role in bioactivity,especially influencing the pharmacological or pharmacokinetic properties.Due to the special 2-deoxy structure,it is a challenge to construct the 2,6-dideoxy glycoside bond in an efficient and stereoselective manner.Herein,a mild and efficient method has been developed for the synthesis of alkyl 2,6-dideoxy-O-glycosides under the catalysis of FeCl3,an economic and environmentally-friendly catalyst.Peracetylated 2-deoxy rhamnose was chosen as starting material for its convenient preparation and great stability.The method could be applied to a wide range of substrates,including primary alcohols,secondary alcohols,tertiary alcohol,complex alcohols such as menthol,steroids,amino acid derivatives,and even sugar derivatives.Morever,the current method has some other advertanges such as short reaction time(5-40 min),good to excellent yields(70-97%),preponderant ?-selectivity(?:?(?)4:1).2.Aryl 2,6-dideoxy-O-glycosides are common components of microbial metabolites.However,examples of synthesizing aryl 2,6-dideoxy-O-glycosides are uncommon except for a few scattered reports.Aryl 2,6-dideoxy-O-glycosidic linkage is more difficult to construct for the electron-withdrawing properties of aromatic rings itself and the readily rearrangement from the O-aryl glycosides to C-aryl glycosides.Based on the results of alkyl 2,6-dideoxy-O-glycosides,a practical protocol for the stereoselective synthesis of aryl 2,6-dideoxy-O-glycosides has been developed in the presence of FeCl3.A series of aryl 2,6-dideoxy-O-glycosides(18 examples)were obtained in mediate to excellent yields within 20 minutes.It was worth mentioning that all the products were obtained with the sole a-selectivity.3.Angucycline antibiotics have shown a wide range of biological activities.However,no one has been developed into clinical drug yet due to toxicity and solubility.Therefore,it is an important task to look for new drug candidates by changing the chemical structure.Practical routes of 2,6-dideoxy 5-aza angucycline analogues were designed and successfully synthesized.Meanwhile,a route for the synthesis of the 2,6-dideoxy-a-D-glucoside glycosyl donor was also developed in eight steps,which was shorter,more economical and environmentally-friendly when compared with the existing synthesis method.