Design, synthesis and characterization of unnatural neurotransmitter amino acid-based peptides

Abstract

Gababutin, an unnatural γ-amino acid, is protected with Boc-group (Boc Gbn-OH) that shows different kind of conformation. To synthesize the unnatural γ-amino acid, I have started with cyclopentanone which is the precursor compound for synthesis of my target compound that is “gababutin”. The precursor compound, cyclopentanone reacts with triethyl phosphonoacetate generally by modified Wittig reaction (Horner Emmons modification) to give exclusively E-alkene product. Here it gives an ester, which undergoes Michael addition on reaction with nitromethane to give nitro compound. Then the nitro compound is reduced using hydrogen gas over activated palladium charcoal and at the final stage the reduced product gives spiro lactam and hydrolysis results into the formation of gababutin. The target compound, gababutin is followed by Boc protection to form ultimate Boc-protected gababutin based unnatural amino acid (Boc-Gbn-OH). All synthesized compounds have been purified by using column chromatography method and characterized by the mass spectrometry and nuclear magnetic resonance (NMR) spectroscopic techniques.