An Efficient Chemoenzymatic Approach towards the Synthesis of Rugulactone

Abstract

Rugulactone is a natural product isolated from the plant Cryptocarya rugulosa. It has shown very important biological activity as an inhibitor of the nuclear factor κB (NF-κB) activation pathway. A new chemoenzymatic approach towards the synthesis of rugulactone is presented here. The chirality, induced to the key intermediate by a stereoselective enzymatic reduction utilizing NADPH-dependent ketoreductase, is described in detail.

Evaluation of a Microreactor for Flow Biocatalysis by Combined Theory and Experiment

“…In this area of research, the spatial compartmentalization and cascading of reaction steps are increasingly exploited for chemical transformations in microfluidic reactors . Here the synthesis of drugs with multiple stereocenters is a prime example of how cascaded biocatalytic or chemoenzymatic reaction sequences can be used for efficient, scalable production processes …”

Recent Advances in the Stereoselective Total Synthesis of Natural Pyranones Having Long Side Chains

“…The compound was found to inhibit constitutive NF-kB activity in human lymphoma cell lines. Several syntheses of rugulactone (48) have recently been reported [38][39][40][41][42][43][44][45][46][47][48]. In these syntheses, the chirality has been introduced by applying different methodologies such as Jacobsen's hydrolytic kinetic resolution of epoxides, Keck/Maruoka asymmetric allylation, chemoenzymatic process, the chiral pool approach, and allylation with chiral boronic esters.…”

“…The latter on treatment with AcOH yielded natural rugulactone (48). In another chemoenzymatic synthesis of rugulactone (48), chirality was induced by a stereoselective enzymatic reduction of a ketoester employing NADPH-dependent ketoreductase [40].…”