Two synthetic approaches to boehmeriasin A are described. A gram scale racemic preparation is accompanied by an efficient preparation of both the pure enantiomers using the conformationally stable 2-piperidin-2-yl acetaldehyde as starting material. The anti-proliferative activity in three cancer cell lines (CEM, HeLa and L1210) and two endothelial cell lines (HMEC-1, BAEC) indicates promising activity at the nanomolar range. Topoisomerases and SIRT2 are identified as biological targets and the experimental data has been supported by docking studies.

Halogen bonding is nowadays a consolidated tool in chemistry. Only recently, the importance of halogen bonding has been demonstrated also in biological systems, owing to the presence of halogens in drugs.This interaction is due to the anisotropy of the electron density around the halogen that leads to the formation of the 'σ-hole', which is responsible for the interaction with a nucleophile site. Unfortunately, classical force fields used in the study of ligand-receptor systems *The Manuscript Click here to view linked References 2 are not able to describe the 'σ-hole'. Here, we propose a pseudo-atom based methodology able to correctly describe halogen bonding involving chlorine using classical force field.

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The synthesis of the eight stereoisomers of 6-[2-methoxy-3-(piperidinyl)propyl]-5,6-dihydropyran-2-one is reported. The configuration at C2′ and C6 is induced by a sterecontrolled allylation reaction with DIP-Cl. The general structure is the result of merging the structures of two natural products (pironetin and dumetorine) with the aim of discovering a new scaffold for tubulin binders. Docking studies and biological evaluations confirm the validity of the approach