A synthesis of (aR,7S)-(−)-N-acetylcolchinol and its conjugate with a cyclic RGD peptide |
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| Authors: | Gilbert Besong Indu Dager Eric Sliwinski F. Thomas Boyle |
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| Affiliation: | a School of Chemistry and Institute of Process Research and Development, Leeds University, Leeds LS2 9JT, UK
b AstraZeneca Pharmaceuticals, Mereside, Alderley Edge, Cheshire SK10 4TG, UK |
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| Abstract: | 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. |
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| Keywords: | Colchicine Suzuki-Miyaura cross-coupling Biaryl Asymmetric reduction RGD peptide |
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