The ritterazine class of natural products comprises 26 compounds-all of which are spiroketal-containing steroidal heterodimers-that inhibit the proliferation of cultured human cancer cell lines with IC50 values in the low nanomolar range. Little is known about their chemistry, cellular target(s), or mechanism(s) of growth inhibition, due primarily to the small amount of material available from natural sources. In this paper we report syntheses of the eastern halves of ritterazines B, F, G, and H and address the energetic and mechanistic aspects of spiroketal equilibration for each. These studies have led to reassignment of the 5,5-spiroketal stereochemistry of ritterazines B and F, and they have enabled us to propose a quantitative description of the natural distribution of these ritterazine compounds.