Enantioselective synthesis of (+)-aspercyclide A

Abstract

An efficient synthesis of the natural IgE-FceRI PPI inhibitor (+)-aspercyclide A (1) was achieved through the use of a Krische iridium-catalyzed diastereo- and enantioselective alkoxyallylation to form the key mono-protected anti-diol intermediate 4, in high optical purity. A derivative of the natural product (15), containing an oxathiazine dioxide ring in place of the ring-A hydroxyaldehyde unit has also been prepared and found to display comparable ELISA activity to the parent compound, indicating that the aldehyde group is not the key determinant of activity.