Ring-Opening of Glycerol Cyclic Phosphates Leads to a Diverse Array of Potentially Prebiotic Phospholipids

Phospholipids are the primary constituents of cell membranes across all domains of life, but how and when phospholipids appeared on early Earth remains unknown. Previously described prebiotic pathways leading to complex phospholipids relied upon preexisting substrates, the availability of which on early Earth has yet to be shown. Here we describe potentially prebiotic syntheses of a diverse array of complex phospholipids and their building blocks. Firstly, we show that choline could have been produced on early Earth by stepwise N-methylation of ethanolamine. Secondly, taking a systems chemistry approach, we demonstrate that the intrinsically activated glycerol-2,3-cyclic phosphate undergoes ring-opening with combinations of prebiotic amino alcohols to yield complex phospholipid headgroups. Importantly, this pathway selects for the formation of 2-amino alcohol-bearing phospholipid headgroups and enables the accumulation of their natural regioisomers. Thirdly, we show that dry-state ring-opening of cyclic lysophosphatidic acids leads to a range of self-assembling lysophospholipids. Our results provide new prebiotic routes to key intermediates on the way towards modern phospholipids and illuminate the potential origin and evolution of cell membranes.