Highly Efficient Synthesis of Monodisperse Poly(ethylene glycols) and Derivatives through Macrocyclization of Oligo(ethylene glycols)

Abstract

A macrocyclic sulfate (MCS)-based approach to monodisperse poly(ethylene glycols) (M-PEGs) and their monofunctionalized derivatives has been developed. Macrocyclization of oligo(ethylene glycols) (OEGs) provides MCS (up to a 62-membered macrocycle) as versatile precursors for a range of monofunctionalized M-PEGs. Through iterative nucleophilic ring-opening reactions of MCS without performing group protection and activation, a series of M-PEGs, including the unprecedented 64-mer (2850 Da), can be readily prepared. Synthetic simplicity coupled with versatility of this new strategy may pave the way for broader applications of MPEGs.

Diazido macrocyclic sulfates as a platform for the synthesis of sequence-defined polymers for antibody drug conjugates

“…While this benzyl alcohol suites our applications well, it should be noted that a wide range of nucleophiles are compatible with this ring opening procedure. 27 Flexibility in type of nucleophile is an additional advantageous feature of this synthesis as it could allow for the installation of wide range of functionalities at the beginning of the polymerization process. The ring opening of the AzMCS monomer using 1,4 propargyloxy benzyl alcohol proceeded with a high yield of 79%, and the pure product was rapidly obtained via flash chromatography ( Fig.…”

“…In this work, we offer a new strategy for the support-free synthesis of chemically defined polymers based on the iterative, stepwise polymerization of azide-functionalized, macrocyclic sulfate monomers. Inspired by the work of Jiang and coworkers, 27 we envisioned that incorporation of an azide into an ethylene glycol (EG) macrocycle ( Fig. 1 ) would allow for the efficient synthesis of sequence-defined oligoethylene glycols that could be functionalized with a desired payload.…”

Striving for Uniformity: A Review on Advances and Challenges To Achieve Uniform Polyethylene Glycol

“…However, several other reported studies were able to overcome this loss of yield, always ensuring high yields, being more prone to successful employment in industry. 17,39,43,52 2.3. Monoprotection.…”

“…108,115 sity. [14][15][16][17]35,41,42,45,[51][52][53]57,58,116 Moreover, comparing with other techniques, this is the one that can provide more useful information about polymer end-group analysis. PEG can be easily ionized via adduct formation with alkali metal ions due to the oxygen-rich nature of this polymer.…”

Expanding the toolbox of metabolically stable lipid prodrug strategies

“…After 5 min, the ice bath was removed and stirred at rt for 30 min. A solution of 5-(trityloxypentyl 4-methylbenzenesulfonate (Zhang et al, 2015;Lahav et al, 2017) (2, 5.3 ml, 5.9 mmol, 1.0 equiv) in anhydrous DMF (4 ml) was then added at rt and stirred overnight. The following morning, the reaction was cooled to 0 °C, quenched with the slow addition of saturated ammonium chloride, and then extracted with EtOAc.…”