Piperidine → L-Glutamic Acid

Participants

Reaction Steps

Approximately 10 mg of Fmoc-Glu-Fib-Trityl-chloride resin was treated with 20% (v/v) piperidine in DMF (2 mL×1 min, filtered, then 2 mL×5 min), filtered and washed (NMP). 4-(Fmoc-aminomethyl)benzoic acid (P/N: Fluka, 04062; 10 eqv to Glu-Fib amount on the resin) was individually activated with HATU (P/N: Applied Biosystems 4317033, 9.5 eqv) and N,N-Diisopropylethylamine (30 eqv) in NMP (˜1 mL), added to the resin and mixed for 30 min. Resin was then filtered, washed with NMP, and the Fmoc group was cleaved. Piperazine acetic acid-TFA salt (10 eqv) was then activated using HATU (9.5 eqv) and N,N-Diisopropylethylamine (60 eqv) in NMP (˜1.5 mL) and added to the resin. After 30 min resin was washed with NMP followed by CH3CN. Conjugated peptide was cleaved (and deprotected) from resin using 95:5 TFA-water (200 μL, 2 h) and precipitated using Et2O. Analysis of compound (39) (see FIG. 30) was performed using ES-MS (direct infusion in water, Calculated [M+H]+=1829.8, Observed [M+H]+=1829.9)

Provenance & Evidence