Syntheses of the Eastern Halves of Ritterazines B, F, G, and H, Leading to Reassignment of the 5,5-Spiroketal Stereochemistry of Ritterazines B and F

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.