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A formal total synthesis of the potent antitumour antibiotic CC-1065 ( I ) is described; both the cyclopropapyrroloindole (2) and the 'dimeric' pyrroloindole (3) are synthesized by routes involving vinyl azide chemistry. The cyclopropapyrroloindole (2) is prepared from 5benzyloxy-2-bromoacetophenone (Schemes 3-5), the key steps being the formation of both indoles by decomposition of the azides (9) and (1 3). The dimer (3) is prepared by coupling the monomeric pyrroloindoles ( 25) and (27), followed by functional group transformations (Scheme 7).The antibiotic CC-1065 (l), isolated from Streptomyces zelensis in 1978 by workers at the Upjohn Company,'V2 is one of the most potent antitumour agents k n ~w n . ~-~ On treatment with alkali, CC-1065 (1) is degraded into two fragments, the cyclopropapyrroloindole (2), variously referred to as the lefthand-or A-unit or as CPI, and the 'dimeric' pyrroloindole (B/cunit) (3) (Scheme 1).6 The dimer (3) is also known as PDE-I dimer because of its relationship to the naturally occurring phosphodiesterase inhibitors PDE-I (4) and PDE-I1 (5). Since the alkaline fragmentation is also the obvious retrosynthetic disconnection for CC-1065 (l), and because of the potent biological activity of the antibiotic, the pyrroloindoles CPI(2), PDE-I (4)' and PDE-I1 (5) have been the subject of intense synthetic Our own work in this area has centred on the use of vinyl azide chemistry to construct the pyrrole/indole rings, and has resulted in the successful total synthesis of the pyrroloindoles PDE-I (4) and PDE-I1 (5),32 the cyclopropapyrroloindole CPI (2),33 and PDE-I dimer (3).34 We now report the full details of this work which constitutes a formal total synthesis of CC-I065 PDE -1 ( 4 ) PDE-I1 ( 5 ) (l), in which, interestingly, all six ring nitrogen atoms are derived, ultimately, from sodium azide. Results and DiscussionSynthesis of the Left-hand Cyclopropapyrroloindole Unit.-The basis of our synthetic approach to the pyrroloindoles PDE-I (4) and PDE-I1 (5) was the thermal decomposition of azidocinnamates, readily prepared from aromatic aldehydes. In 'd C C -1 0 6 5 (1) l o. -n CPI ( 2 ) PDE -I Dimer (3) Scheme 1.

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