Synthesis of 2-oxo amide triacylglycerol analogues and study of their inhibition effect on pancreatic and gastric lipases

A general method for the synthesis of chiral 2-ore amide triacylglycerol an alogues, from (R)- or (S)-3-aminopropane-1,2-diol, was developed. These nov el inhibitors of digestive lipases are analogues of the triacylglycerol mol ecule, a natural substrate of lipases, and they were designed to contain th e Zero amide functionality in place of the scissile eater bond at the sn-1 or sn-3 position and nonhydrolysable ether bonds instead of ester bonds at the other two remaining positions. The 2-ore amide derivatives synthesised were tested for their ability to form stable monomolecular films at the air /water interface by recording their surface pressure/molecular area compres sion isotherms. The inhibition of porcine pancreatic and human gastric lipa ses by the 2-ore amides was studied by means of the monolayer technique wit h mixed films of 1,2-dicaprin and with variable proportions of each inhibit or. The alpha (50) values of these triacylglycerol analogues for PPL and HG L varied between 4.4 to 7.0% and 5.6 to 15.9%, respectively. The chirality at the sn-2 position of Zero amide triacylglycerol analogues affected the a ,, value for HGL, but not for PPL.