EFFICIENT SYNTHESIS OF THE PHARMACOPHORE OF THE HIGHLY POTENT ANTITUMOR ANTIBIOTIC CC-1065

The pharmacophore CPI (3) of the potent antitumor antibiotic CC-1065 ( 1) was synthesized in a very short reaction sequence of 11 steps with an overall yield of 23 %. The key steps are two consecutive cyclizatio ns mediated by organotransition metal complexes, which form first the pyrroline and then the pyrrole ring in 3. Thus, halogen metal exchange of the N,N'-bisallylbromobenzene with rBuLi and subsequent reaction w ith Cp2ZrMeCl gave 11 as a single product in 60 % yield after quenchin g with two equivalents of iodine. Transformation of the iodomethyl gro up in 11 into an acetoxymethyl group, followed by Heck reaction, isome rization, and reductive cleavage, provided the pyrroloindoline system 4, which was converted into 3.