Cyclic Poly(α-peptoid)s by Lithium bis(trimethylsilyl)amide (LiHMDS)-Mediated Ring-Expansion Polymerization: Simple Access to Bioactive Backbones

Abstract

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Superfast and Water‐Insensitive Polymerization on α‐Amino Acid N‐Carboxyanhydrides to Prepare Polypeptides Using Tetraalkylammonium Carboxylate as the Initiator

“…We propose that the NCA polymerization in this study could be initiated by nucleophilic addition of carboxylate 1 to C5‐carbonyl on a NCA to form the transition state TS1 and open the NCA ring to generate compound 2 that has an N‐terminal carbamate anion as the reactive center to undergo a further nucleophilic addition to the C5‐carbonyl of another NCA and form the transition state TS2 . It is worth mentioning that such nucleophilic attack of carbamate mechanism has been reported in the synthesis of small molecule mixed anhydrides [18] and the recent report on polymerization of N ‐substituted NCA to prepare cyclic polypeptoids [19] . Then chain propagation happens at one concerted step with decarboxylation of the RNHC(=O)O − and nucleophilic attack of N to the carbonyl on a NCA ring to form compound 3 .…”

Superfast and Water‐Insensitive Polymerization on α‐Amino Acid N‐Carboxyanhydrides to Prepare Polypeptides Using Tetraalkylammonium Carboxylate as the Initiator

“…We propose that the NCApolymerization in this study could be initiated by nucleophilic addition of carboxylate 1 to C5-carbonyl on aNCA to form the transition state TS1 and open the NCAring to generate compound 2 that has an N-terminal carbamate anion as the reactive center to undergo afurther nucleophilic addition to the C5-carbonyl of another NCAa nd form the transition state TS2.I ti sw orth mentioning that such nucleophilic attack of carbamate mechanism has been reported in the synthesis of small molecule mixed anhydrides [18] and the recent report on polymerization of N-substituted NCAt op repare cyclic polypeptoids. [19] Then chain propagation happens at one concerted step with decarboxylation of the RNHC( = O)O À and nucleophilic attack of Ntothe carbonyl on aNCA ring to form compound 3.S uch ac oncerted addition and decarboxylation reaction pathway allows the in situ decarboxylation and direct amide bond formation at the same time to extend the polymer chain. Thec ontinuous polymerization will give product 4 bearing aC-terminal Rgroup from the initiator and an N-terminal carbamate group,w hich undergoes hydrolysis of the anhydride and decarboxylation during polymer purification to afford product 5.…”

An Inspection into Multifarious Ways to Synthesize Poly(Amino Acid)s

“…Bonduelle and co-workers synthesized cyclic polypeptoids by lithium bis(trimethylsilyl)amide-mediated polymerizations of NNCAs. [58] Barz and co-workers and Heise and co-workers synthesized various star-like PAAs by multifunctional initiators. [59,60] The star-like PAAs served as nanocarriers in mucosal drug delivery [61] and delivery of small interfering RNAs (siRNAs) [59] and DNAs.…”