Nucleoside Analogues with a 1,3‐DieneFe(CO) 3 Substructure: Stereoselective Synthesis, Configurational Assignment, and Apoptosis‐Inducing Activity

Abstract The synthesis and stereochemical assignment of two classes of iron‐containing nucleoside analogues, both of which contain a butadieneFe(CO) 3 substructure, is described. The first type of compounds are Fe(CO) 3 ‐complexed 3′‐alkenyl‐2′,3′‐dideoxy‐2′,3′‐dehydro nucleosides (2,5‐dihydrofuran derivatives), from which the second class of compounds is derived by formal replacement of the ring oxygen atom by a CH 2 group (carbocyclic nucleoside analogues). These compounds were prepared in a stereoselective manner through the metal‐assisted introduction of the nucleobase. Whilst the furanoid intermediates were prepared from carbohydrates (such as methyl‐glucopyranoside), the carbocyclic compounds were obtained by using an intramolecular Pauson–Khand reaction. Stereochemical assignments based on NMR and CD spectroscopy were confirmed by X‐ray structural analysis. Biological investigations revealed that several of the complexes exhibited pronounced apoptosis‐inducing properties (through an unusual caspase 3‐independent but ROS‐dependent pathway). Furthermore, some structure–activity relationships were identified, also as a precondition for the design and synthesis of fluorescent and biotin‐labeled conjugates.