TOTAL SYNTHESIS AND BIOLOGICAL PROPERTIES OF NOVEL ANTINEOPLASTIC (CHLOROMETHYL)FURANOINDOLINES - AN ASYMMETRIC HYDROBORATION MEDIATED SYNTHESIS OF THE ALKYLATION SUBUNITS

(chloromethyl)-5-hydroxy-8-methyl-3H-furano[3,2-e] indole (CFI) as a n ovel re; placement of the cyclopropylpyrroloindoline (CPI) alkylation subunit of CC-1065, U-71184, and U-73975 (adozelesin) has been synthes ized and incorporated into a series of efficacious antineopIastic agen ts. A partial solution to an asymmetric synthesis of the CFI alkylatio n subunit has been achieved by the implementation of an asymmetric hyd roboration reaction of an intermediate 3-methyleneindoline (13). Exten sion to the asymmetric synthesis of the CBI and CI alkylation subunits is presented. The demonstration and comparative study of the sequence -selective DNA alkylation properties of the CFI-based agents are detai led, and the preliminary in vitro and in vivo antineoplastic propertes of these agents in the human epidermoid cell lung carcinoma (T222) ar e described.