Synthesis of Novel (S)-N-Boc-3-Pyrazolylalanine-Derived α-Amino Acids

Di-tert-butyl (S,E)-4-[(dimethylamino)methylidene]-5-oxopyrrolidine-1,2-dicarboxylate (1), available in three steps from L-pyroglutamic acid, was used as the starting material for the preparation of a small library of N-Boc-protected 3-pyrazolylalanine tert-butyl esters 3 using 'ring-switching' strategy with different hydrazine derivatives 2. Acid-catalyzed deprotection (TFA/CH2Cl2) of 3 yielded free amino acids 4 isolated as dihydrochloride salts, while selective deprotection with HCl/EtOAc furnished N-Boc deprotected tert-butyl esters dihydrochlorides 5. Hydrolysis under basic conditions furnished N-Boc-protected amino acid 6.

Read article: Heterocycles, 2015, 91, 2315-2326