Crystallographic determination of stereochemistry of biologically active 2″,3″-dibromo-7-epi-10-deacetylcephalomannine

The stereochemistry at C2″ and C3″ of two diastereomers of 2″,3″-dibromo-7-epi-10-deacetylcephalomannine (6 and 7), which were synthesized by reacting 7-epi-10-deacetylcephalomannine (5) with bromine, were assigned unambiguously based on crystallographic studies of 6. The X-ray crystallographic analysis shows that 6 adopts an absolute configuration of (2″S,3″R), and 7 can be assigned as (2″R,3″S) configuration. The side-chain conformation of 6 was revealed to be different with the known hydrophobic collapse and the apolar conformations, as found in solid state and in solution. However, most side-chain torsion angles of 6 were found to be very similar to those of tubulin-bound T-shaped conformation (T-Taxol). Both 6 and 7 showed strong in vitro paclitaxel-like activity.