Convergent synthesis of polyether ionophore antibiotics: Synthesis of the spiroketal and tricyclic glycal segments of monensin

Article abstract of DOI:10.1021/ja00069a013

The syntheses of the spiroketal II and tricyclic glycal III portions of the polyether antibiotic monensin (I) are described. The butyric acid side chain of spiroketal II is constructed through either Sharpless epoxidation of a cis-2-butenol residue or by Brown crotylation of an α-methylacetaldehyde unit. The spiroketal is then generated through a hetero-Diels-Alder addition between a tetrahydropyranoid methylene ketone and acrolein. Finally, [6.5]-spiroketal structure II is prepared by mild acid catalyzed rearrangement of [6.6]-spiroketal epoxide 23. Glycal III was made from the C/D subunit 44. This subunit was prepared by the ester enolate Claisen rearrangement that unites the tetrahydrofuranoid C and D rings 40 and 41 by Brown crotylation, Wittig condensation, and then cyclization to form the E ring. The synthesis of the two fragments set the stage for a final ester enolate Claisen rearrangement that will form the skeleton of the polyether monensin (I).