1987 Volume 40 Issue 9 Pages 1316-1324
Optically active 15-deoxyspergualin (II) and 15-deoxy-ll-O-methylspergualin (IIa) were synthesized, and their antitumor activities were examined. The (-)-enantiomers of both II and Ha were active against mouse leukemia LI 210, while the (+)-enantiomers were almost inactive. The optical resolution of the key intermediate, (±)-N-(7-guanidinoheptanoyl)-α-alkoxyglycine (VI) was achieved by use of an exopeptidase, serine (acid) carboxypeptidase [EC 3.4.16.1] and (±)-N-(7-guanidinoheptanoyl)-α-alkoxyglycyl-L-amino acid (VIII) as the substrate. Considering the enzymatic susceptibility of the substrate (VIII), we deduced that the absolute configuration of the carbon at 11 (C-11) of the bioactive (-)-enantiomer, and so that of natural spergualin (I), is S. This is, to our knowledge, the first report of the use of carboxypeptidase for the resolution of N-acyl amino acid.
