Abstract: A ctinomycin D(AMD) contains a planar phenorazone ring as well as two cyclic depsipeptides and is best known for its effectiveness as an inhibitor of transcription. It has been used clinically for treating Wilm's tumor, gestational chriocarcinoma. Although it possesses valuable biological activities its high cytotoxity and inactivities toward some tumors have prompted the search for modified AMD. On the basis of the result of AMD-DNA binding model proposed by Takusagawa, we designed and synthesized 5,5'-Val₂-AMD and 2,2'-Phe₂AMD. The title compounds were synthesized from 3 in 13 steps with overall yield of 27%, 17%, respectively. The structures were identified with ¹H NMR, 2D NMR, MS and HRMS. The biological activities of two analogs were carried out in comparison with those of AMD. The order of antitumor activity was 2,2'-Phe₂-AMD>AMD>5,5'-Val₂-AMD.

Key words: Synthesis, Bioactivity, 5,5'-Val₂-AMD, 2,2'-Phe₂-AMD