Synthesis of library from amino-hydroxy substituted cyclopentanes

Based on radical induced carbocyclisation of unsaturated aldonolactones our group has elaborated procedures for the preparation of several amino-hydroxy substituted cyclopentane derivatives [1]. These highly functionalized molecules are suitable for attachment to solid phase and subsequent parallel synthesis. This protocol was investigated in collaboration with TransTech Pharma, USA, and a series of diversified molecules with a range of functionalities have been prepared. Figure 1 Amino-hydroxy substituted cyclopentanes prepared from carbohydrate starting material The compounds I and II (fig 1) could easily be anchored to PS-resin through the hydroxyl functionalities, forming acetals stable to the subsequent reaction conditions. Then several methods for modification of the amine functionality were investigated, such as reductive amination, sulfonylation and Ugi-reactions. Especially the Ugi-reaction followed by an opening of the lactone with an amine posed to be a suitable protocol for diversification (fig 2). Figure 2 Reactions performed on solid phase In this way several compounds were synthesized by parallel synthesis and cleaved off the resin. TransTech Pharma has tested these compounds in biological assays of interest to the company; these results will be presented in the poster. [1] S.K. Johansen, H. Kornøe, I. Lundt, Synthesis, 1999, 1, 171-177. S.K. Johansen, I. Lundt, J.Chem. Soc. Perkin Trans. 1, 1999, 3615-3622.