N-Succinimidyl chloroformate

Protocol for the Activation of PEG with N-Succinimidyl Chloroformate or NjAF-Disuccinimidyl Carbonate... 

Dissolve 6 mmol of either N-succinimidyl chloroformate or N,N -disuccinimidyl carbonate (Aldrich) in 10 ml of dry acetone. 

React for 2 hours if activating with N-succinimidyl chloroformate or 6 hours if using N,N -disuccinimidyl carbonate. Maintain stirring with a magnetic stirring bar. 

If N-succinimidyl chloroformate was used, filter out the white precipitate of 4-(dimethylamino) pyridine hydrochloride using a glass fiber filter pad. Collect the supernatant. 

A modification of the Zalipsky method by Miron and Wilchek (1993) simplifies the creation of the succinimidyl carbonate-activated species. Instead of using highly toxic phosgene to form a chloroformate intermediate and then reacting with NHS, the new procedure utilizes either N-hydroxysuccinimidyl chloroformate or N,N -disuccinimidyl carbonate (DSC Chapter 4, Section 1.7) to produce the succinimidyl carbonate—PEG in one step (Fig. 380). Since both activation reagents are commercially available, creating an amine-reactive PEG derivative has never been easier. 

Figure 380 An alternative route to an succinimidyl carbonate derivative of mPEG can be accomplished by the reaction of the terminal hydroxyl group of the polymer with either N,N -disuccinimidyl carbonate or N-hydroxysuccinimidyl chloroformate.

As alternatives to 4-nitrophenyl chloroformate, carbonyl diimidazole [100-102] or di-A-succinimidyl carbonate [103,104] can be used to convert polymeric alcohols into alkoxycarbonylating reagents suitable for the preparation of support-bound carbamates. Polystyrene-bound alkoxycarbonyl imidazole is less reactive than the corresponding 4-nitrophenyl carbonate, and sometimes requires heating to undergo reaction with amines. Additional activation of these imidazolides can be achieved by N-methylation (Entry 9, Table 14.7). 

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