Enzymatic synthesis of C-terminal arylamides of amino acids and peptides.
A mild and cost-efficient chemo-enzymatic method for the synthesis of C-terminal arylamides of amino acid and peptides is described. Using the industrial serine protease Alcalase under near-anhydrous conditions, C-terminal arylamides of N-Cbz-protected amino acids and peptides could be obtained from the corresponding C-terminal carboxylic acids, methyl (Me) or benzyl (Bn) esters, in high chemical and enantio- and diastereomeric purities. Yields ranged between 50% and 95% depending on the size of the aryl substituents and the presence of electron-withdrawing substituents. Complete alpha-C-terminal selectivity could be obtained even in the presence of various unprotected side-chain functionalities such as beta/gamma-carboxyl, hydroxyl, and guanidino groups. In addition, the use of the cysteine protease papain and the lipase Cal-B gave anilides in high yields. The chemo-enzymatic synthesis of arylamides proved to be completely free of racemization, in contrast to the state-of-the-art chemical methods.
Nuijens
Timo
T
DSM Pharmaceutical Products, Innovative Synthesis & Catalysis, P.O. Box 18, Geleen 6160 MD, The Netherlands.
Cusan
Claudia
C
Kruijtzer
John A W
JA
Rijkers
Dirk T S
DT
Liskamp
Rob M J
RM
Quaedflieg
Peter J L M
PJ
D000577:Amides / Q000737:chemistry* / Q000378:metabolism*; D000596:Amino Acids / Q000737:chemistry*; D000813:Anilides / Q000737:chemistry / Q000378:metabolism; D001407:Bacillus / Q000201:enzymology; D008049:Lipase / Q000378:metabolism; D008968:Molecular Conformation; D010206:Papain / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D013237:Stereoisomerism; D013381:Subtilisins / Q000378:metabolism*
D000577:Amides; D000596:Amino Acids; D000813:Anilides; D010455:Peptides; D008049:Lipase; D013381:Subtilisins; D010206:Papain