Synthesis of a para-quinone macrolactam related to geldanamycin by ring closing metathesis

Model studies conducted with the α,β,γ,δ-unsaturated 3-alkenyl-2,4,5-trimethoxyanilides revealed that a ring closing metathesis (RCM) of these compounds is possible if the ansa chain contains more than 14 atoms. The (Z)-configurated products were obtained in good yields (77–87%) and with perfect simple diastereoselectivity. Since the oxidation of the 2,4,5-trimethoxyanilides led predominantly to undesired ortho-quinones such as or to para-azaquinones such as the macrocyclic 2,5-di-iso-propoxy-4-methoxyanilide was prepared. The iso-propyl protecting groups could be selectively cleaved and the intermediate para-hydroquinone oxidized on air to the desired para-quinone (86% yield). The compound shows some key features (macrolactam ring with the same ring size, α,β,γ,δ-unsaturated anilide, para-quinone) of geldanamycin.