Abstract
The 1,3-dipolar cycloaddition of nitrile imines to 11-aryl-4-(arylmethylidene)-1,2,3,4,11,11a-hexahydrodibenzo[
b
,
e
][1,4]thiazepines possessing exocyclic C=C and endocyclic C=N bonds as dipolarophilic sites showed site selectivity, depending on the type of C-substituent in the nitrile imine. 1,3-Dipolar cycloaddition of
C
-aryl nitrile imines occurred selectively to the exocyclic C=C bond, whereas the endocyclic C=N bond was involved in the cycloaddition with
C
-ethoxycarbonyl nitrile imines. A combination of total energy and molecular orbital plots for the highest occupied and lowest unoccupied molecular orbitals was used to verify the proposed reaction mechanisms and stereoselectivity. Some of the isolated products exhibited moderate to good antitumor activity. The results of POM analysis of the relative cytotoxicity of these new derivatives in comparison to Doxorubicin are also reported.