The role of the hydroxymethyl function on the biological activity of the antitumor antibiotic sparsomycin

Abstract The synthesis is described of the sparsomycin analogues 11–14 from the l -amino acids valine, isoleucine, phenylalanine and proline, respectively. The sparsomycin derivative 21 was not prepared in a similar way from glycine, but from cystamine following a different reaction route. These analogues, as well as the O -methylated and O -acetylated derivatives 15 and 16 , respectively, were tested in vitro for their protein synthesis inhibitory activity and for their inhibition of colony formation of murine leukemia L1210 cells. The results of these assays indicate that the hydroxymethyl function of 1 is not essential for its biological activity, and that increase of lipophilicity in this “northern” region of 1 does not noticeably affect the activity of the drug.