N-Benzoyl-L-leucinol

The coupling reaction of benzoic acid and nicotinic acid hydrazides with N- protected L-amino acids including valine, leucine, phenylalanine, glutamic acid and tyrosine is reported. The target compounds, N-Boc-amino acid-(N;-benzoyl)- and N- Boc-amino acid-(N;-nicotinoyl) hydrazides 5a-5e and 6a-6e were prepared in very high yields and purity using N-[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl- methylene]-N-methyl-methanaminium hexafluorophosphate N-oxide (HATU) as coupling reagent. The antimicrobial activity of the Cu and Cd complexes of the designed compounds was tested. The products were deprotected affording the corresponding amino acid-(N;-benzoyl) hydrazide hydrochloride salts (7a-7e) and amino acid-(N;- nicotinoyl) hydrazide hydrochloride salts (8a-8e). These compounds and their Cu and Cd complexes were also tested for their antimicrobial activity. Several compounds showed comparable activity to that of ampicillin against S. aureus and E. coli.

Two phenylhexane derivatives (1, 2), benzoylergostane (3), N-benzoyl-L-leucine methyl ester (4), two known ergostanes, and highly degraded incisterol were isolated from fruit bodies of Agaricus blazei. Compound 3 exhibited strong cytotoxicity toward HepG2 cells (IC(50) = 6.0 ± 0.33 μM).

Dynamic kinetic resolution (DKR) was demonstrated in the carbodiimide-mediated couplings of N-benzoyl-DL-amino acids with L-amino acid esters: the yields of the D-L-peptides significantly exceeded 50% in some cases. N-Benzoyl-DL-t-leucine afforded the D-L-peptide almost exclusively (up to 96% yield) in the reaction with methyl L-prolinate, which is the most efficient DKR obtained in the field of amino acids and derivatives.