Total synthesis of cucurbitoside-like phenolic glycosides by double fluorous and acyl mixture synthesis

The first and simultaneous total syntheses of cucurbitosides A, B, G, and I, seguinosides C and D, and two unnatural analogs were achieved using the technique of fluorous mixture synthesis. The eight precursors of cucurbitoside-like phenolic glycosides were prepared by glycosylation of a mixture of two glucopyranosyl acceptors bearing different fluorous benzyl groups with a mixture of four apiofuranosyl donors bearing benzoyl, 3-methylbutyryl, 4-benzyloxybenzoyl, and 4-nitrobenzoyl groups, followed by a single run of HPLC with serially connected Fluophase® RP and Inertsil® ODS-3 columns. Finally, the individual pure disaccharide precursors were detagged to yield the eight cucurbitoside-like phenolic glycosides.