Efficient synthesis of 2-methylene-4-phenyl-1,3-dioxolane, a cyclic ketene acetal for controlling the NMP of methyl methacrylate and conferring tunable degradability

Abstract

The efficient and reliable synthesis of 2-methylene-4-phenyl-1,3-dioxolane (MPDL) was reported and MPDL was used as a controlling comonomer for nitroxide-mediated polymerization of methyl methacrylate to give degradable copolymers.

Degradable polymer prodrugs with adjustable activity from drug-initiated radical ring-opening copolymerization

“…Oligo(ethylene glycol) methyl ether methacrylate (MeOEGMA, M n = 300 g mol –1 ), styrene (S, 99%), methyl methacrylate (MMA, 99%) and toluene (anhydrous, 99.8%) were purchased from Sigma-Aldrich (France) and used as received (except for MMA which was distilled under reduced pressure). 2-Methylene-4-phenyl-1,3-dioxolane (MPDL), 54 4-amino-1-[4-( tert -butyl-dimethylsilanyloxy)-5-( tert -butyl-dimethyl-silanyloxymethyl)-3,3-difluorotetrahydro-furan-2-yl]-1 H -pyrimidin-2-one (TBDMS-Gem), 15 alkoxyamines Gem-AMA-SG1 ( ref. 10 ) and AMA-digly 11 were prepared as reported elsewhere.…”

Degradable Copolymer Nanoparticles from Radical Ring-Opening Copolymerization between Cyclic Ketene Acetals and Vinyl Ethers

“…2-methylene-1,3-dioxepane (MDO) monomer was prepared by adapting a previously published method, using the cyclic bromoacetal as intermediate. 31 Alkyne-MePEG 750 was prepared according to a previous report. 30 Diethylazobisisobutyrate (DEAB) was kindly supplied by Arkema.…”

Tunable Degradation of Copolymers Prepared by Nitroxide-Mediated Radical Ring-Opening Polymerization and Point-by-Point Comparison with Traditional Polyesters

“…Recently, our group revisited the use of 2-methylene-4-phenyl-1,3-dioxolane (MPDL) by optimizing its synthesis 23 and using it as a comonomer during the NMP of either OEGMA 24 or MMA 23 to make degradable PEG-based or PMMA-rich materials, respectively ( Figure 1). Even though NMP of methacrylic esters is known to be relatively difficult to achieve, the styrene-like open radical structure of MPDL allowed good control and high living chain fractions to be achieved during its copolymerization with methacrylic esters by acting as a so-called 'controlling' comonomer.…”

“…24 As for P(MMA-co-MPDL) copolymers, insertion of MPDL only moderately affected the glass transition temperature compared to pure PMMA, while giving low molar mass degradation products after hydrolysis. 23 In these studies, copolymer degradation was performed under accelerated conditions to probe the presence of open CKA units; in aqueous 5% KOH for OEGMA-based copolymers and in THF/MeOH solution with 5% KOH for MMA-based counterparts. Degradation kinetics were rapid (from minutes to hours) and allowed to confirm the presence of labile groups in the copolymer backbones.…”