ISOLATION AND SYNTHESIS OF NOVEL FARNESYL-PROTEIN TRANSFERASE INHIBITORS, VALINOCTIN-A AND VALINOCTIN-B, FROM STREPTOMYCES STRAIN MJ858-NF3

Two novel farnesyl protein transferase inhibitors, valinoctins A (1) a nd B (2), were isolated from the fermentation broth of Streptomyces st rain MJ858-NF3. The tentative structures of these compounds were eluci dated from NMR and mass spectra as dipeptides consisting of valine and a novel amino acyl moiety. Four possible isomers of valinoctin A were synthesized, and the protected derivative of the appropriate compound was crystallized to give the relative stereochemistry of X-ray analys is. Since the valine residue of valinoctin A was determined to be the L-configuration by a chiral HPLC column, absolute configuration of val inoctin A was determined.