A fully synthetic route to the papulacandins. Stereo-specific spiroacetalization of a C-1-arylated methyl glycoside.

Lewis acid-catalyzed, hetero Diels-Alder reaction of (E)-1-methoxy-3-trimethylsilyloxy-1,3-butadiene with 6-benzoyloxymethyl-2,4-dibenzyloxy benzaldehyde afforded 2-(6-benzoyloxymethyl-2,4-dibenzyloxyphenyl)-2,3-dihydro-4H- pyran-4-one. This was converted into a derivative of papulacandin D by a stereo-specific, spiroacetalization of a C-1 methoxylated aryl glycoside, [3,5-dibenzoyloxy-(methyl 3-O-acetyl-4,6-di-O-benzoyl-DL-glucopyranosid-1-yl)phenyl]methyl benzoate.