Organic Chemistry of Drug Synthesis. Volume 7

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

4. OTHER BENZOFUSED CARBOCYCLIC COMPOUNDS 79