Study On Selective Acylation Of Hydroxyl Based On Green Catalytic System

Due to the complex spatial structure of carbohydrates which existence of multiple hydroxyl groups with similar activities.It is inevitable that complex and cumbersome protection and de-protection operations are used in the synthesis and modification of carbohydrate compounds.Therefore,the design of excellent protection and protection group strategies is the core issue of carbohydrate research.Selective protection could realize the targeted protection of hydroxyl groups,which greatly improves the reaction efficiency and plays an important role in the synthesis of carbohydrate compounds.Meanwhile,acyl group is the most widely used hydroxyl protection group due to its advantages of easy introduction and removal,mild reaction conditions and so on.In recent years,a variety of selective acylation methods for hydroxyl groups have been developed,all of which have both advantages and disadvantages.If a catalytic system is evaluated from multiple dimensions such as wide application range of substrates,green economy,mild reaction conditions,simple operation and high reaction efficiency,the ideal catalyst and method that can meet the above requirements has not been developed at present.In this thesis,the following contents were studied in exploring the use of green and efficient catalysts for selective acylation of hydroxyl groups:1.One-pot carbohydrate hydroxyl protection strategy was developed based on the efficient selective silylation and selective acylation.In this study,in order to realize the priority protection of primary hydroxyl group,an efficient selective silylation method for diols and polyols containing primary hydroxyl group was developed,and obtained the silylated products of primary hydroxyl group with85-95%isolated yields.The DMF was proved to be a good catalyst for silylation by mechanism study.Further combination of this method with the selective acylation method previously developed in our lab can achieve the one-pot silylation and acylation protection of carbohydrate hydroxyl groups,which enables the efficient synthesis of 3-O-acyl and6-O-silicyl substituted orthogonally-protected building blocks under mild conditions.2.Selective acylation of hydroxy catalyzed by iron(?)reagentsIn order to solve the problem that realize selective protection of hydroxy under green and mild conditions to distinguish the reactivity of secondary hydroxyl groups in carbohydrates.In this study,a green and efficient catalyst,iron acetylacetone[Fe(acac)₃],for the selective acylation of 1,2-diols,1,3-diols and glycosides containing cis-diol was developed successfully.The method has the advantages of mild reaction conditions and economical and green catalyst.It is speculated that the five-member ring intermediate formed between iron reagent and diols under base conditions is the key to achieve high selectivity in this reaction.The catalytic effect of iron reagent on selective acylation was further investigated,and the ferric chloride can be used as a good catalyst for selective benzoylation of substrates mentioned above with the assistance of acetylacetone(Hacac)ligand was confirmed,the reaction selectivity and reactivity were similar to or slightly worse than Fe(acac)₃ catalytic effect in most cases.The method developed in this study is more economical and greener,and this result provides the possibility to further explore the effects of combinations of different metal salts and ligands on selective protection strategies.3.Selective acylation of hydroxy catalyzed by stannous chlorideAccording to the above research strategy,the effects of combinations of different metal salts and ligands in order to obtain the best catalytic system for a wider range of selective protection strategies were further explored.Based on this,the highly efficient hydroxyl selective acylation method using Sn Cl₂ as a catalyst was developed,which has a wider substrate range,including the use of iron catalyst limited glycosides containing trans-diols.Sn Cl₂ has a series of advantages as a catalyst,such as simple structure,inexpensive and easy to obtain,green and low toxicity.When the dosage of Sn Cl₂ is reduced to 1 mol%,it still shows a high catalytic activity.4.A quasi-one-pot strategy for hydroxyl protection of carbohydrates was developed based on Sn Cl₂-catalyzed acetalization and selective acylationIn this study,Sn Cl₂ can be used to catalyze the acetalization of unprotected glycoside substrates was proven firstly.Combining with the results of the selective acylation catalyzed by Sn Cl₂,the quasi-one-pot strategy that continuous acetalization and selective benzoylation of hydroxy was developed for efficient preparation of 2-OH or 3-OH orthogonally-protected glycoside acceptors.It is easy to obtain the acceptors with the reversed protection position by Ag₂O mediated acyl group migration reaction.Furthermore,the blood group antigen analogues were efficiently synthesized using the prepared acceptors as starting material,which proved the application value of this method in oligosaccharide synthesis.In summary,a series of studies on the development of green catalysts for hydroxyl selective acylation have been done in this thesis.Green and easily available catalysts are used in all developed hydroxyl protection methods,which basically conforms to the original intention of this study and has certain theoretical research significance and practical application value.