Synthetic studies towards cryptolaevilactone M from d-glucose

This article describes the synthetic studies towards cryptolaevilactone M from naturally occurring D-(+)-glucose. The ten step synthetic strategy includes the construction of key α,β-unsaturated δ-lactone core from C-3 PMB protected d-glucose diacetonide. Highly diastereoselective indium-mediated allylation provided C-allyl intermediates at the C-5 position in 94% yield. Acryloylation and Grubbs II-catalyzed ring-closing metathesis furnished the δ-lactone in 92% yield. Selective anomeric oxidation challenges were overcome using PCC of C-2 TBS protected δ-lactone, giving the required gluconolactone in good yields. Although low yield, but Grignard addition delivered the desired adduct introducing the phenyl 1-butene side chain of cryptolaevilactone M establishing the core framework of the target molecule. The resulting intermediate is suitably constructed for final steps toward cryptolaevilactone M, which are underway. This strategy not only enables efficient access to cryptolaevilactone M, but also establishes a versatile route to related bioactive δ-lactones.