PEGylation by Reductive Amination

Other methods for the preparation of 4 have been published, mainly in the patent literature. For example, it has been claimed that 2-naphthalenesulfonyl chloride reacts with 2,2-dimethyl-l,3-dioxolane-4-ethanol, yielding synthetic intermediate sulfonate 27 (Equation 3.10). Sulfonate 27 was then reacted with the mPEG alkoxide to afford a protected mPEG-diol derivative 28, which after hydrolysis under acid conditions, followed by oxidation with NalO, gave mPEG-propionaldehyde 4 in good yield (Equation 3.10) [124]. 

Diethylacetals 29a and 29b are more stable and can be obtained with higher purities than the mPEG-aldehydes 26 and 4. Hence, it has been indicated that 29a and 29b are 

Baker and coworkers introduced 2-methylpropionaldehyde mPEG derivative 30 and successfully used this reagent for the site-selective conjugation of interferon P-la. mPEG aldehyde 30 can be easily prepared by a three-step procedure that affords the reagent in excellent yield (Equation 3.12) [136]. 

Noteworthily, this conjugate has completed phase 3 clinical trials and has been submitted for FDA approval for the treatment of multiple sclerosis (Plegridy ). 

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