Synthesis of polyphosphodiesters by ring‐opening polymerization of cyclic phosphates bearing allyl phosphoester protecting groups

Abstract

The allyl phosphoester group is shown to be a protecting group for the synthesis of anionic polyphosphodiesters. Our strategy relies on the synthesis of a cyclic phosphate monomer bearing a pendant allyl phosphoester group, its easy purification by fractional distillation, its organocatalyzed ringopening polymerization by 1,8-diazobicyclo[5.4.0]undec-7-ene (DBU) and 1-[3,5-bis(trifluoromethyl)phenyl]-3-cyclohexyl-thiourea (TU). Finally, the deprotection of the allyl phosphoester group is carried out by reaction with sodium benzenethiolate in the absence of any detectable degradation.

High definition polyphosphoesters: between nucleic acids and plastics

“…Excellent hydrophilicity is obtained with phosphodiesters, and these can be produced from allyl triesters by treatment with sodium thiophenolate. 155 This circumnavigates the base-lability of the cyanoethyl group used in solid phase phosphoramidite synthesis, which could be problematic given that 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is used at a catalytic component in polymerisation. Despite the lack of charge, short-side chained polyphosphotriesters such as poly(ethyl ethylene phosphate) (PEEP) are water soluble themselves, enabling them to act as hydrophilic components of block copolymers.…”

Polyphosphoesters: New Trends in Synthesis and Drug Delivery Applications

“…By this reaction, a range of cyclic phosphotriester having R′ = H and various R groups that include alkyl chains of various size (methyl to octyl) and unsaturated chains (allyl, butenyl, butynyl, acrylate) has been obtained in good purity enough to be polymerized by the ROP process. However, the purification of these monomers that are highly sensitive toward traces of water or other protic species that easily open the ring, remains a tedious step.…”

“…Water‐soluble negatively charged polyphosphodiesters are also attractive polyelectrolyte materials. They can be achieved by selective hydrolysis of the pendant side chain which is a quite challenging reaction as the backbone integrity should be preserved. Interestingly, poly(phosphotriester) bearing allyl pendant groups can be easily converted into such polyelectrolyte by simple nucleophilic reaction, the allyl group playing the role of protecting group in this case (Scheme ).…”

“…They can be achieved by selective hydrolysis of the pendant side chain which is a quite challenging reaction as the backbone integrity should be preserved. Interestingly, poly(phosphotriester) bearing allyl pendant groups can be easily converted into such polyelectrolyte by simple nucleophilic reaction, the allyl group playing the role of protecting group in this case (Scheme ). This deprotection can be achieved quantitatively in very mild conditions and does not require acidic conditions, which prevents the prematured degradation of the poly(phosphate) chain.…”

An Efficient Thermal Elimination Pathway toward Phosphodiester Hydrogels via a Precursor Approach

“…For those cases, a precursor route based on a different phosphotriester prepolymer elimination method is highly desirable. In the literature, a few methods have been described to effect this transformation ranging from dealkylation by triethylamine8 or thiophenolate,20,21 hydrolysis under acidic conditions,7 oxidation by dinitrogen tetroxide22,23 to the retro‐Michael condensation13,24 method widely used in nucleoside synthesis. Thermolytic routes that do not require the addition of any chemicals and proceed in neutral media have also been described, both in polymer science25 as in oligonucleoside synthesis 26.…”