Stereoselective Desymmetrization of 2,2‐Bishydroxymethyl‐1‐tetralones by Iodocyclization, Synthesis of Novel Enantiopure [6.6.5] Tricyclic Framework and Chemoenzymatic Diversity Generation

Abstract

Stereoselective halocyclization of prochiral 2,2-bishydroxymethyl-1-tetralone derivatives with N-halosuccinamides afforded an interesting tricyclic scaffold found in many naturally occurring hasubanan alkaloids. Enantiopure tricyclic scaffolds are synthesized by using enzymatic kinetic resolution (EKR) of the parent racemic compound. Microbial ketoreductase (Geotrichum candidum, Aspergillus niger and Candida parapsilosis) mediated stereoselective reduction reactions have been successfully employed to these enantiopure tricyclic scaffolds which, followed by functional group manipulation, provides novel cyclic frameworks.