The synthesis of xestobergsterol A, a unique pentacyclic steroid with potent antihistamine activity and the synthesis of biologically active structural analogues

The first total synthesis of xestobergsterol A is reported. We have utilized the Breslow remote functionalization technique and also a selective intramolecular aldol condensation to synthesize natural xestobergsterol A and 7-deoxyxestobergsterol A, along with a variety of structural analogues. Structural analogues containing a cholesterol sidechain were prepared from commercially available cholesterol in very few steps to produce active structural analogues of the xestobergsterols which may prove to be useful antihistamine drugs. We also determined the C/D ring cis:trans stabilities for a variety of 15-ketones prepared and this allowed us to determine the structural requirements that allow us to predict whether the cis or trans C/D ring junction will be more stable.