Technical Abstract: A 14-step biomimetic synthetic route to glyceollin I in ca. 1.5% overall yield has been developed. In addition to being useful for the elaboration of analogs that can contribute to SAR, this route provides practical access to analytical standards that may be used for quality control purposes when glyceollin I is obtained naturally from stressed soy bean. For the latter, the use of asymmetric NMR shift reagents and chiral HPLC have been shown to be convenient methods for preliminary and final assessments of enantiomeric excess. Both enantiomers, as well as the glyceollin I racemate, were studied in antiproliferation studies using hormone-related human cancer cell lines. Within the breast and ovarian cell culture panel, all three of the glyceollin I forms exhibit substantial growth inhibitory (GI) effects on estrogen receptor negative (ER-) and ER+ cell lines at concentrations in the low to mid µM range. At similar concentrations within the prostate cancer cell culture panel, natural and racemic glyceollin I have a greater GI effect on androgen receptor positive (AR+) LNCaP cells than the AR- PC3 and DU145 cell lines. Although not pronounced, there appear to be subtle differences between the glyceollin I enantiomers in their overall GI profiles. Perhaps more importantly, however, the composite of these studies suggest that the overall antiproliferative properties exhibited by the glyceollin I stereoisomers may be derived from a more complicated mechanistic picture than can be explained by relying upon just the classical types of interactions with ERs.