Exploration Of Solid Phase Synthesis Of [n]Rotaxane

Rotaxane is a class of interlocking supramolecular molecule formed by a ring of molecules(hosts)nested on a dumbbell-shaped linear axis molecules(guests).In natural and synthetic system,a large number of studies have been conducted on several types of host compounds such as crown ethers,cyclodextrins,and macrocyclic amides.If multiple cyclic ring molecules are located on one linear axis,it becomes a polyrotaxane.Pseudorotaxane is distinguished from a rotaxane by the lacking of terminal bulky groups of the linear axis,which forms a dynamic equilibrium of free or bonded state of the host molecule on the axis.As similar as polyrotaxane,if multiple cyclic molecules are included,it forms a polypseudortaxane.Over the past 50 years,researches on rotaxane and other mechanical interlocking molecules(MIMs)have been the focus of supramolecular materials scientists.Due to their unique mechanical interlocking structure,pesudorotaxane and polyrotaxnes have exhibited unique material properties and potential applications,for example,construction of functional molecular machines with complex structures or functional polymeric materials.Usually,[n]rotaxane is synthesized stepwise in the liquid phase.The steps of synthesizing [n]rotaxane is cumbersome,time consuming and normally subject to multiple separations and purifications resulting in low yield.Currently the synthesis of polyrotaxane is mainly formed by cyclodextrin(CD)as host molecule and polymer chain as guest molecule such as polyethylene glycol(PEG)in the liquid phase.The resulting pseudopolyrotaxne is normally a nonuniform disperse system,which can be end-capped affording polyrotaxne.How to efficiently synthesize [n]rotaxane with a presise molecular structure and can be diversified conviently is still a challenging subject in the application of supramolecular polymer systems.Currently solid phase synthesis is mainly used in the field of peptides and nucleic acids synthesis.It is an efficient synthetic technology for conducting multi-step reactions continuously without the separation of intermediates on a solid support.Combining our research interesting on peptide materials with rotaxane-based materials,this thesis intends to explore the solid phase synthetic strategy of [n]rotaxane by employing rotaxane as repeating unit.The macrocyclic amide or crown ether macrocyclic molecule are used as the host molecules to synthesize the rotaxane monomer either in the liquid phase or on the solid phase,and then the rotaxane monomer is covalently attached to the solid phase surpport using Fmoc-Chemistry to synthesize [n] rotaxane.Finally,we successfully synthesized a [2]rotaxane monomer based on crown ether as host macrocycle in the liquid phase,which was then used to synthesize a [3]rotaxane on the solid support and characterized by LCMS.The synthesis of [n]rotaxane on the solid phase can precisely control the number of rotaxane units,and conviently modify the synthesized [n]rotaxane with functional molecules to prepare molecular-scale polymers with specific structure and function.This type of supramolecular polymer is expected to be used as biocompatible material in fields such as tissue engineering or drug delivery systems.