INHIBITORS OF LIPID PHOSPHATIDATE RECEPTORS - N-PALMITOYL-SERINE AND N-PALMITOYL-TYROSINE PHOSPHORIC-ACIDS

An improved synthesis of two lipid phosphoric acids, N-palmitoyl-L-ser ine phosphoric acid (NP-Ser-PA) and N-palmitoyl-L-tyrosine phosphoric acid (NP-Tyr-PA), from the benzyl esters of L-serine and L-tyrosine is described. The sequence of N-acylation, followed by phosphitylation w ith N,N-diisopropyl dibenzyl phosphoramidite, oxidation to the corresp onding phosphate triesters, and simultaneous debenzylation of the dibe nzyl phosphate and benzyl carboxylic esters gave NP-Ser-PA and NP-Tyr- PA in high overall yields. NP-Ser-PA and NP-Tyr-PA and their D stereoi somers were potent reversible inhibitors of the lysophosphatidic acid receptors expressed in Xenopus oocytes, thus providing prototypic stru ctures for the development of inhibitors of the lysophosphatidate fami ly of phospholipid growth factors.