Modification of proline‐based 2,5‐diketopiperazines by anionic ring‐opening polymerization

Abstract

2,5-Diketopiperazines (DKPs) are the smallest cyclic dipeptides found in nature with various attractive properties. In this study, we have demonstrated the successful modification of proline-based DKPs using anionic ring-opening polymerization (AROP) as a direct approach. Four different proline-based DKPs with various side chains and increasing steric hindrance were used as initiating species for the polymerization of 1,2-epoxybutane or ethoxyethyl glycidyl ether in the presence of t-BuP 4 phosphazene base. The addition of a Lewis acid, tri-isobutyl aluminum, to the reaction mixture strongly decreased the occurrence of side reactions. Impact of the DKP side-chain functionalities on molar mass control and dispersity was successfully evidenced.

pH‐Sensitive Poly(ethylene glycol)/Poly(ethoxyethyl glycidyl ether) Block Copolymers: Synthesis, Characterization, Encapsulation, and Delivery of a Hydrophobic Drug

“…mPEG‐ b ‐PEEGE copolymers were synthesized by anionic ring‐opening polymerization using mPEG‐ t BuP 4 as initiating system ( Figure A). mPEG hydroxyl end‐groups were deprotonated by t BuP 4 phosphazene base, generating extremely reactive alcoholates associated with phosphazenium cations, which initiated the polymerization of EEGE monomers . Molar masses determined by size exclusion chromatography and 1 H NMR are in good agreement with the theoretical ones ( Table 2 ).…”

“…mPEG hydroxyl end-groups were deprotonated by tBuP 4 phosphazene base, [47] generating extremely reactive alcoholates associated with phosphazenium cations, which initiated the polymerization of EEGE monomers. [48,49] Molar masses determined by size exclusion chromatography and 1 H NMR are in good agreement with the theoretical ones ( Table 2). The polymerization degree of the hydrophobic EEGE block is defined by the [M] 0 /[I] 0 ratio, allowing the control of the copolymer hydrophilic-hydrophobic balance.…”

Synthesis of Macrocyclic Poly(glycidyl phenyl ether) with an Inverted-Dipole Microstructure via Ring Closure of Two-Arm Linear Precursors Obtained by Initiation witht-BuP4/Water

“…We also observed that in that polymerization system, coinitiation from residual water was sometimes unavoidable, even by working with utmost care . This undesired initiation has been frequently found in polymerization systems catalyzed by t -BuP 4 . , …”

Alternating copolymerization of bio-based N-acetylhomocysteine thiolactone and epoxides

“…hydrogen and a conjugated carbonyl moiety, which were likely to react with the anionic propagating centers. [31][32][33] However, no interferences with the mechanism of the alternating polymerization have been evidenced. With the help of a 1 H- 15 N heteronuclear single quantum correlation (HSQC) NMR spectrum, the large 1 H NMR signal between 6.8 and 7.6 ppm could be attributed to NH of the unmodified acetamido groups (Figure 2).…”

“…It was previously demonstrated that higher amount of phosphazene base favor the occurrence of side-reaction due to an increase the propagating center reactivities. [32][33] A polymerization in the bulk at 90°C resulted in high dispersity polymer (Table 1, run 6). In order to increase the M n , a reaction was performed at 60°C by increasing the ([NHTL] 0 +[tBuGE] 0 )/[ROH] 0 ratio (Table 1 run 9, X n,targeted = 80).…”