The Cobalt Way to Angucyclinones: Asymmetric Total Synthesis of the Antibiotics (+)-Rubiginone B₂, (−)-Tetrangomycin, and (−)-8-O-Methyltetrangomycin

摘要

A cobalt(I)-mediated convergent and asymmetric total synthesis of angucyclinones with an aromatic B ring has been developed. In the course of our research, we synthesized three naturally occurring anguclinone derivatives, namely, (+)-rubiginone B₂ (1), (−)-8-O-methyltetrangomycin (2), and (−)-tetrangomycin (3). By combining 3-hydroxybenzoic acid, 3-methoxybenzoic acid, citronellal, and geraniol as starting materials in a convergent way, we were able to synthesize chiral triyne chains, which were cyclized with [CpCo(C₂H₄)₂] (Cp=cyclopentadienyl) by means of an intramolecular [2+2+2] cycloaddition to their corresponding tetrahydrobenzo[a]anthracenes. Successive oxidation and deprotection steps led to the above-mentioned natural products 1–3.