4. OTHER BENZOFUSED CARBOCYCLIC COMPOUNDS
Multidrug resistance, as noted earlier, is the all too prevalent phenomenon
where a patient’s resistance to one class of cancer chemotherapy agents
comes to encompass mechanistically quite different drugs. Compounds
with a wide variety of structural features have shown at least preliminary
activity in resolving this problem. The structurally rather complex agent
zosuquidar ( 87 ) has shown promising activity against this problem.
Reaction of dibenzosuberone ( 80 ) with the difluorocarbene from chlorodi-
fluoroacetate affords the cyclopropyl adduct ( 81 ). Reduction of the ketone
with borohydride proceeds to afford the derivative wherein the fused
cyclpropyl and alcohol are on the same side of the seven-membered ring.
O
80
ClCF 2 CO 2 Na
O
81
F F
NaBH 4
OH
82
F F
SOCl 2
Cl
F F
NCH=O
HN
N
F F
NH
83
84
N
OH
N
O O
85
86
TsO O
FF N N
N
O
OH
87
- OTHER BENZOFUSED CARBOCYCLIC COMPOUNDS 79