Studies towards the total synthesis of Herbimycin A

摘要

Herbimycin A (1) belongs to the ansamycin family and is a 19-membered lactam with seven stereogenic centres, making it a synthetic challenge, which was first isolated in 1979 by Omura et al. Herbimycin A (1) exhibits a broad spectrum of biological activities: herbicidal, inhibitor of angiogenesis and of the maturation of growth factor receptor tyrosine kinases.ududFigure 1 - Herbimycin A (for figure see pdf)ududSince its discovery, only three total syntheses of Herbimycin A (1) have been described in the literature, along with the syntheses of advanced fragments.ududThis thesis describes a new route to Herbimycin A (1), using a wide range of chemical reactions than those used in the previous routes from the literature.ududThe main idea is to split Herbimycin A (1) into an aromatic fragment and an aliphatic fragment as shown below in Scheme 1.ududScheme 1 - Retrosynthesis highlighting both aromatic and aliphatic fragments (for figure see pdf)ududThe synthesis of aliphatic fragment (4) follows up the work of Ansell and Pietsch, past members of the Parsons group.udInteresting results could be obtained and a wide range of Organic Chemistry reactions could be investigated.