Design, synthesis and evaluation of two diastereoisomeric phosphonate inhibitors of lamb pregastric lipase

A mixture of the two diastereoisomers of (2R)-1,2-di-O-butyl-sn-glycerol-3-O-p-nitrophenyl-n-propylphosphonate, varying only in their configuration at phosphorus, was synthesised from (R)-3-O-benzyl-sn-glycerol. The diastereoisomers were separated by normal phase HPLC and fully characterised. Both diastereoisomers were irreversible inhibitors of the activity of lamb pregastric lipase (LPGL), although the isomer which eluted first in the HPLC separation was significantly more effective.