DETERMINATION OF THE RELATIVE AND ABSOLUTE STEREOCHEMISTRY OF FOSTRIECIN (CI-920)

The absolute stereochemistry of fostriecin (1, CI-920), a potent antit umor antibiotic presently in Phase I clinical trials at NCI, was deter mined to be 5R,8R,9R,11R. 2D H-1-H-1 NMR. NOE experiments conducted on the cyclic phosphate derivative 2 and acetonide revealed a syn-diol s tereochemical relationship between C8 and C9 and an anti-diol stereoch emical relationship between C9 and C11, respectively. The 5R absolute configuration assignment was confirmed by synthesis of the degradation product 8 previously disclosed. Additional degradation studies of 1 t o provide 7 and chiral-phase HPLC comparison with a sample of known ch irality established the absolute stereochemistry of C11 to be R. This, along with the relative stereochemical assignments established the fu ll set of absolute stereochemistry assignments for 1.