Determination of the Relative and Absolute Stereochemistry of Fostriecin (CI-920)

The absolute stereochemistry of fostriecin ( 1, CI-920), a potent antitumor antibiotic presently in Phase I clinical trials at NCI, was determined to be 5 R,8 R,9 R,11 R . 2D 1 H− 1 H NMR NOE experiments conducted on the cyclic phosphate derivative 2 and acetonide 4 revealed a syn -diol stereochemical relationship between C8 and C9 and an anti -diol stereochemical relationship between C9 and C11, respectively. The 5 R absolute configuration assignment was confirmed by synthesis of the degradation product 8 previously disclosed. Additional degradation studies of 1 to provide 7 and chiral-phase HPLC comparison with a sample of known chirality established the absolute stereochemistry of C11 to be R . This, along with the relative stereochemical assignments established the full set of absolute stereochemistry assignments for 1 .