A synthesis of (aR,7S)-(−)-N-acetylcolchinol and its conjugate with a cyclic RGD peptide

An asymmetric synthesis of (−)-N-acetylcolchinol is described based on a Suzuki–Miyaura coupling to generate the biaryl pharmacophore. The sole asymmetric centre was introduced by an asymmetric reduction of a dibenzosuberone derivative 24 using lithium borohydride in the presence of stoichiometric amounts of a chiral Lewis acid (TarB–NO2). A conjugate between an αVβ3 integrin-binding cyclic peptide c[RGDfK] and colchinol (adipoyl linker) was synthesised with an aim to deliver colchinol to solid tumours selectively.