Methods for preparing polymeric reagents and compositions of polymeric reagents
View Patent ↗Methods for preparing active carbonate esters of water-soluble polymers are provided. Also provided are other methods related to the active carbonate esters of water-soluble polymers, as well as corresponding compositions.
1. A synthetic method comprising:
(a) combining a composition comprising an aprotic solvent and a hydroxy-terminated, water-soluble polymer having the following structure:
CH 3 O—(CH 2 CH 2 O) n —CH 2 CH 2 —OH
wherein (n) is an integer from 2 to about 4000, with a composition comprising di(1-benzotriazolyl) carbonate, wherein the composition comprising the di(1-benzotriazolyl) carbonate is added such that there is an excess of the di(1-benzotriazolyl) carbonate relative to the hydroxy-terminated, water-soluble polymer, to thereby result in a composition comprising an active carbonate ester of the water-soluble polymer having the following structure:
wherein (n) is an integer from 2 to about 4000, and unreacted di(1-benzotriazolyl) carbonate;
(b) adding a composition comprising a reactive molecule selected from the group consisting of water, a lower alkyl monohydric alcohol, hydrogen sulfate and a lower alkyl monobasic amine to the composition comprising the active carbonate ester of a water-soluble polymer and unreacted di(1-benzotriazolyl) carbonate, wherein the composition comprising the reactive compound is added such that substantially all of the unreacted di(1-benzotriazolyl) carbonate is substantially consumed; and
(c) reacting the active carbonate ester of a water-soluble polymer lysine to form a polymeric lysine derivative.
2. The method as in claim 1 , wherein the reactive molecule is selected from the group consisting of water, a lower alkyl monohydric alcohol, hydrogen sulfide, and a lower alkyl monobasic amine.
3. The method as in claim 1 , wherein the reactive molecule is selected from hydroxyalkyl attached to a solid support, mercaptoalkyl attached to a solid support, primary amine attached to a solid support, and secondary amine attached to a secondary support.
4. The method as in claim 1 , wherein the polymeric lysine derivative has the following structure:
wherein each (n) is an integer from 2 to about 4000.