Controllable glycosylation of polyphosphazene via radical thiol–yne click chemistry

Abstract

We describe a versatile approach to synthesize glycosylated polyphosphazenes with controllable density of glycosyl groups. These glycopolymers have been synthesized by the nucleophilic substitution of poly(dichlorophosphazene) with propargylamine and subsequent “thiol–yne” click reaction between poly[di(propargylamine)phosphazene] and 2,3,4,6‐tetra‐O‐acetyl‐1‐thio‐β‐D‐glucopyranose (SH‐GlcAc4). The polymers were characterized with FTIR and 1H NMR. We found that the high steric hindrance of SH‐GlcAc4 plays a key role in the overall reaction process, and ∼55% of the alkyne groups participate in the “thiol–yne” click reaction. About 8% of the alkyne groups convert to alkene groups at the end of click reaction. The substitution of alkyne/alkane mixture was conducted to reduce the alkyne density in the side groups of polyphosphazenes and minimize the influences of this steric effect. Mixed‐substituent polyphosphazene was synthesized with 2:3 ratio of alkyne and alkane. In this case, almost no alkyne group remains after the “thiol–yne” click reaction, and thus the glycosylated polyphosphazene is able to form into micelles through self‐assembly process. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Radical Thiol‐yne Chemistry on Diphenylacetylene: Selective and Quantitative Addition Enabling the Synthesis of Hyperbranched Poly(vinyl sulfide)s

“…mechanism in Figure 2 ). To further probe the selectivity of this reaction, the thiol-to-alkyne ratio was increased to 5:1 and under both thermal and photochemical conditions (2 h reaction times), the major product was again the mono-addition product, i.e., vinyl sulfi des (entries [8][9][10][11][12][13]. Only under very forcing conditions, extended reaction time (20 h) and a large excess of thiol (10 equiv.…”

A versatile approach to the synthesis of polyphosphazene derivatives via the thiol–ene reaction

“…In our previous study, we reported that steric effects played an important role during the photochemical reaction of polymers with high local densities of alkyne groups and thiols 19. This conclusion also applies to PBAAP.…”

“…Although the thiol–yne reaction allows for the addition of two thiol molecules to an alkyne, significant steric effects can preclude some alkynes from reacting with two thiol molecules 19,22. Alternatively, the thiol–ene coupling reaction is another type of thiol‐based radical addition reaction 23.…”

Polyphosphazenes for the delivery of biopharmaceuticals

“…need to go through protection/deprotection procedures for their nucleophilic substitution on PDCP. Fortunately, an extensive library of PPZs has been developed, including derivatives substituted with alkene, alkyne, or vinyl groups, for example, allylamine, 2‐aminoethyl methacrylate, allyl glycinate, methacrylic acid, and propargylamine derivatives. These PPZs with alkene and alkyne side chains can be used as secondary precursors for free‐radical polymerization .…”