Implicit in these data is that the occurrence in modern phospholipid headgroups of the 2-amino alcohol motif present in Ch, EA and its methylated derivatives, Ser and Thr, might not have been coincidental, but was rather predicated by the intrinsic reactivity of these nucleophiles. Selection of phospholipid headgroup isomers. Though the ring-opening of G>P with amino alcohols produces both phosphodiester regioisomers (G3PXs and G2PXs), the product distribution changed over time. For example, in the reaction of G>P with EA, the non-natural phospholipid headgroup isomer, G2PE, initially formed more readily than its natural counterpart, G3PE (Fig. and). However, after three weeks 31 P-NMR analysis indicated that the G2PE peak had markedly decreased in intensity, relative to that of the G3PE peak, and continued doing so. By contrast, the natural regioisomer G3PE accumulated for ten weeks. Importantly, the same trend was observed for all other GPXs (Fig. ).