Methods of synthesizing and using derivatives of [2-(2-aminoethoxy)ethoxy] acetic acid

Abstract

A synthetic reaction to produce [2-(2-aminoethoxy)ethoxy] acetic acid (AEEA) derivatives. This synthetic reaction does not require isolation and purification of intermediates. The AEEA derivatives can be used to synthesize high load polystyrene-polyethylene glycol-like resins having excellent swelling characteristics.

1 - 36 . (canceled)  
     
     
         37 . A resin comprising at least one PEG-like chain, wherein the PEG-like chain comprises 1- to 10-mer of [2-(2-aminoethoxy)ethoxy]-acetic acid (AEEA), AEEA derivatives, or combinations thereof.  
     
     
         38 . The resin of  claim 37 , wherein the resin comprises a polystyrene resin.  
     
     
         39 . The resin of  claim 38 , wherein the polystyrene resin comprises an aminomethylated polystyrene resin.  
     
     
         40 . The resin of  claim 37 , wherein the PEG-like chain comprises 5- to 10-mer of AEEA, AEEA derivatives or combinations thereof.  
     
     
         41 . The resin of  claim 37 , wherein the PEG-like chain comprises 5-mer of AEEA, AEEA derivatives, or combinations thereof.  
     
     
         42 . The resin of  claim 37 , wherein the resin comprises an AEEA content of less than or equal to about 50%.  
     
     
         43 . The resin of  claim 37 , wherein the resin comprises an AEEA content between about 40% and about 50%.  
     
     
         44 . The resin of  claim 37 , wherein the resin comprises a loading capacity of at least about 0.33 mmol/gram.  
     
     
         45 . The resin of  claim 37 , wherein the resin comprises a loading capacity of at least about 0.40 mmol/gram.  
     
     
         46 . The resin of  claim 37 , wherein the resin comprises a loading capacity of at least about 0.54 mmol/gram.  
     
     
         47 . The resin of  claim 37 , wherein the resin comprises a swelling capacity in water of at least about 2.4 milliliters/gram.  
     
     
         48 . The resin of  claim 37 , wherein the resin comprises a swelling capacity of at least 3.8 milliliters/gram in one of acetonitrile or methanol, or of at least 6.0 milliliters/gram in one of N,N-dimethylformamide or dichloromethane.  
     
     
         49 . The resin of  claim 37 , wherein the AEEA derivative comprises an AEEA including a fluorenylmethoxycarbonyl (Fmoc) group, an allyloxycarbonyl (Alloc) group, a tert-butyloxycarbonyl (Boc) group, or a benzyloxycarbonyl (Z) group.  
     
     
         50 . The resin of  claim 49 , wherein the AEEA derivative comprises 1-(9H-fluoren-9-yl)-3-oxa-2,7,10-trioxa-4-azadodecan- 12-oic acid; [2-(2-benzyloxycarbonyl-aminoethoxy)-ethoxy]-acetic acid; [2-(2-tert-butyloxycarbonyl-aminoethoxy)ethoxy]-acetic acid; or [2-(2-allyloxyoxycarbonyl-aminoethoxy)ethoxy]-acetic acid.  
     
     
         51 . The resin of  claim 37 , wherein the AEEA derivative is made by a method comprising: 
 (a) converting 2-[2-(2-chloroethoxy)ethoxy]-ethanol to an azide derivative;    (b) reducing the azide derivative to its corresponding amine;    (c) reacting the amine to obtain an R-derivative, wherein R comprises a suitable protecting group; and    (d) oxidizing the R-derivative to give the [2-(2-aminoethoxy)ethoxy]acetic acid derivative.    
     
     
         52 . The resin of  claim 37 , wherein the PEG-like chain is formed on the resin by a method comprising loading 1-mer of the AEEA derivative thereon.  
     
     
         53 . The resin of  claim 52 , wherein the loaded 1-mer of the AEEA derivative includes an R-group thereon, and wherein the method further comprises removing the R-group from the previously loaded 1-mer of the AEEA derivative and loading thereon another 1-mer of the same or a different AEEA derivative.  
     
     
         54 . The resin of  claim 53 , wherein the removing and loading is repeated up to 9 times.  
     
     
         55 . The resin of  claim 53 , wherein the R-group comprises an allyloxycarbonyl (Alloc) group, a fluorenylmethoxycarbonyl (Fmoc) group, a tert-butyloxycarbonyl (Boc)group, or a benzyloxycarbonyl (Z) group.  
     
     
         56 . A resin comprising at least one PEG-like chain, wherein the PEG-like chain comprises 1- to 10-mer of [2-(2-aminoethoxy)ethoxy]-acetic acid (AEEA), AEEA derivatives, or combinations thereof; wherein the resin comprises a polystyrene resin; and wherein the resin is further characterized by having an AEEA content between about 40% and about 50%, a loading capacity of at least about 0.33 mmol/gram, and a swelling capacity in water of at least about 2.4 milliliters/gram.  
     
     
         57 . A resin comprising more than one PEG-like chain, wherein each of the PEG-like chains comprises 1- to 10-mer of [2-(2-aminoethoxy)ethoxy]-acetic acid (AEEA), AEEA derivatives, or combinations thereof, and wherein each of the PEG-like chains has a defined, identical length.