Diglycolic anhydride

Wang resin was purchased from Advanced ChemTech (1% DVB, 0.70mmol/g substitution, 100-200 mash, Cat. SA5009). Anhydrous tetrahydrofuran (THF), A/A-dimcthyl-formamide (DMF), methanol, dichloromethane, pyridine, 1,1 -carbonyldiimidazole (CDI), piperazine, homopiperazine, trans-1,4-diaminocyclohexane, 4-(dimethylamino)pyridine (DMAP), succinic anhydride, diglycolic anhydride, 3-methyl-glutaric anhydride, 2-aminophenol, 2-amino-p-cresol, 2-amino-4-tert-butyl phenol, /V-methylmorpholine (NMM), triphenylphosphine, diethyl azodicarboxylate (DEAD), and trifluoroacetic acid (TFA) were purchased from Aldrich Chemical Company, Inc. and used without further purification. PyBOP was purchased from Novabiochem. 

Other recent reports of interesting terpolymerization processes involving cyclohexene oxide and diglycolic anhydride or vinylcyclohexene oxide have appeared in the literature [66-68]. These processes are indicated in (7) and (8), and were carried out in the presence of p-diiminate zinc catalysts. The vinyl functionalized polymer was intramolecularly crosslinked by a metathesis reaction to afford nanoparticles. 

As an alternative to the Glu and Asp scaffolds, the A-(dialkyl)amide of diglycolic acid has been proposed (13). This is readily prepared by heating equivalent amounts of diglycolic anhydride and, for example, bis(octadecyl)amine in refluxing toluene for 48 hours followed by recrystallization from chloroform (mp 81-82 °C)J178 In a similar mode, polyoxyethylene of selected chain length has been used to prepare dicarboxylic acids which, upon mono-amidation with bis(alkyl)amines, yield lipo moieties (e.g., 14) that are coupled to selected amine groups of peptides to produce the peptide amphiphiles. 179180 ... 

Scheme 7 Synthesis of twin drugs 71 and 72. Reagents and conditions (a) CO(OCCl3)2, sat. Na2C03aq/CH2Cl2, 0 °C (b) diglycolic anhydride, CH2C12, rt (c) mono-Boc-diamines, DCC, HOBt, DMF (d) TFA, CH2C12 (e) 82, DCC, HOBt (f) H2 (50 psi), Pd/C, MeOH (g) 76, DMF (h) 83, DCC, HOBt, DMF...

A section such as this would be incomplete if it did not refer to some interesting synthetic routes to MA. Hurd and Glass reported that pyrolysis of diglycolic anhydride 3 yielded MA. This method is of more than just historic interest since it provides a built-in potential method of introducing a label in the H, C, or O atoms. 

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