Synthesis And Properties Of Polypeptoids Based On Ugi Multicomponent Reaction Of Amino Acids

Polypeptoids,including ?-,?-,?-,and poly(?-peptoid)s,are structural mimics of polypeptides.In analogy to polypeptides,polypeptoids show good biocompatibility and have been wildly explored for biomedical application.For instance,they can be applied as drug and gene vehicles,bioseparation films,antimicrobial agents,and other therapeutics.The Ugi reaction is a four-component reaction between acid,amine,isocyanide,and aldehyde.Besides the advantages of atom economy,high efficiency,and benign conditions,the Ugi reaction enables the construction of peptoid backbones(e.g.,pentapeptoids).Therefore,because of the possibility to build new libraries of polypeptoids,the Ugi reaction has recently provided a novel platform in polypeptoid chemistry.Therefore,it is important to develop simple,efficient and general methods to synthesize polypeptoids via Ugi reaction.The main results of this dissertation are summarized as follows:1.We describe that natural amino acid monomers as AA'-and BB'-typemonomers can be polymerized via Ugi reaction in a step-growth fashion,which leads to alternating polypeptoids with molecular weight up to 15 kg/mol.These alternating polypeptoids are thermally responsive and exhibit cloud points(Tcp)between 27 and 37?.Importantly,the marriage of high functionality of amino acids with Ugi reaction also enables the preparation of polypeptoids encoding both protected amino and carboxyl groups in the side chains with alternating arrangement.The cleavage of the protecting groups leads to the alternating polyampholytes without any compositional drift.Such alternating polyampholytes not only exhibit high water solubility(>100 mg/mL),but also demonstrate the ability to resist aggregation with proteins.2.We demonstrate that natural lysine and furfural monomers can be polymerized via Ugi reaction in a step-growth fashion,which leads to the polypeptoids with a number average molecular weight(Mn)up to 10.0 kg/mol,under mild conditions(open to air,room temperature,and catalyst free).Importantly,polymerization can be carried out in water,avoiding the use of toxic solvents.The structures of the resultant polypeptoids were confirmed by 1H and 13C NMR spectroscopy.All of the signals attributable to the repeating unit of the polypeptoid that should be produced by the Ugi reaction are visible.Moreover,the MALDI-TOF MS analysis of the resulting product consists of an array of peaks separated by a 407.2 g/mol interval,which corresponds to the molar masses of the repeating unit.The MALDI-TOF MS result is consistent with the proposed mechanism of Ugi reaction.These polypeptoids exhibit a Tg value of 116?,and do not show melting transition.Indeed,the renewable feedstocks and simple concepts described here offer an attractive framework from which the Ugi reaction can be applied to prepare lysine and furfural based polymers.3.In our attempt to develop protecting-group-free polymerization towards poly(amino acid)s that can mimic the exquisite selectivity of enzymes,We synthesized poly(peptide-alt-peptoid)s via the Ugi reaction of dipeptides with isobutyraldehyde and tert-butyl isocyanide,affording alternating peptide-peptoid copolymers with Mn of 14.7 kg/mol and D(Mw/Mn)of 1.47.