Synthesis of CBI-PDE-I Dimer, the Benzannelated Analogue of CC-1065

Article abstract of DOI:10.1021/jo00049a035

A practical synthesis of CBI (2), utilizing inexpensive starting materials, was developed and applied to the synthesis of benzannelated analogs of CC-1065, in particular CBI-PDE-I-dimer (13) and CBI-bis-indole (17).While a Sharpless asymmetric dihydroxylation reaction proved effective at providing optically active intermediates, a more classical resolution procedure was used to prepare materials of higher optical purity.A novel cyclization employing a six-membered-ring intermediate (12) was employed to construct the cyclopropyl ring in CBI.Like CC-1065, CBI-PDE-I-dimer appears to cause delayed toxicity in mice.