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 SuzukieMiyaura 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 (TarBeNO2). A conjugate between an aVb3 integrin-binding cyclic peptide c[RGDfK] and colchinol (adipoyl linker) was synthesised with an aim to deliver colchinol to solid tumours selectively. 2008 Elsevier Ltd. All rights reserved.