Study On Br(?)nsted Phosphoric Acid Mediated Controllable Ring-Opening Polymerization Of NCAs

As an important class of biopolymer materials,peptides have been widely used in biomedical applications such as tissue engineering scaffolds,drug delivery matrices,and biosensor-responsive materials[1]Therefore,the synthesis of polypeptides with a well-defined structure has attracted the attention of researchers.Although remarkable progress has been made in the preparation of well-defined polypeptides by controlled ring-opening polymerization(ROP),under mild conditions,the use of stable catalysts enables the opening of a-amino acid N-carboxylic anhydrides(NCAs),which is still challenging in a relatively short period of time.Here,we investigated the rapid ROP of y-benzyl-L-glutamic acid-N-carboxylic anhydride(BLG-NCA)mediated by a catalytic system consisting of chemically stable Br(?)nsted phosphoric acid and aniline.The(S)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate with 3,3' position was successfully prepared by improving reaction conditions.By optimizing the conditions of the coupling reaction,the 3,3' position of the BINOL have been introduce electron-donating(methyl?methoxy)and electron-withdrawing(perfluorophenyl)substituents,synthesized(S)-3,3'-bis(2-naphthyl)-2,2'-bis(methoxymethyl)-1,1'-binaphthyl.(S)-3,3'-bis(2-naphthyl)-2,2'-bis(methoxymethyl)-1,1'-binaphthyl,(S)-3,3'-bis(methyl)-2,2'-bis(methoxy methyl)-1,1'-binaphthyl,(S)-3,3'-bis(pentafluorophenyl)-2,2'-bis(methoxymethyl)-1,1'-binaphthyl,(S)-3,3'-bis(methoxy)-2,2'-bis(methoxymethyl)-1,1'-binaphthyl.The improvement of the hydrolysis reaction conditions(solvent,temperature,and hydrochloric acid concentration)greatly promoted the hydro lysis efficiency,and free phenolic hydroxyl groups were successfully obtained.Finally,four different substituents of chiral phosphoric acid were successfully prepared by refluxing and chromatographic purification,which is(S)-3,3'-bis(methoxy)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate(3,3'-OCH3-BNPH),(S)-3,3'-bis(2-naphthyl)-1,1'-binaphthyl-2,2'-dihydrogenphosphate(3,3'-C10H7-BNPH),(S)-3,3'-bis(methyl)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate(3,3'-CH3-BNPH),(S)-3,3'-bis(pentafluorophenyl)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate(3,3'-C6F5-BNPH).The absorption intensity value of the carbonyl group in the infrared Glu-NCA as an internal standard.The absorption intensity value is linear to the conversion rate and calculating the conversion rate of polymerization of BLG-NCA.By optimizing the 3,3'substituents of BINOL was excavated to initiate the controlled ROP of BLG-NCA.Optimal reaction conditions,PBLG with Mn = 10.2 kg/mol and D=1.06.By adjusting the feed ratio of the monomer/initiator with a feed of 150:1,PBLG with Mn = 27.8 kg/mol and D=1.08.The polymerization kinetics study showed that the 3,3'-OCH3-BNPH/aniline catalyst system initiated the ROP of BLG-NCA,and the monomer conversion and molecular weight showed a first-order linear relationship(R2=0.9922).The 3,3'-OCH3-BNPH can control the ROP of BLG-NCA with a variety of aniline derivatives and aliphatic primary amines with different functional groups.PBLG with D = 1.08-1.18,showing the catalytic system.The wide applicability.Thus,the catalytic system can provide a platform that can be rapidly prepared for biomedicine.The end-functionalized PBLG and block copolymers.