A STEREOSELECTIVE AND HIGHLY PRACTICAL SYNTHESIS OF CYTOSOLIC PHOSPHOLIPASE A(2) SUBSTRATE, -1-O-HEXADECYL-SN-2-THIOGLYCERO-3-O-PHOSPHOCHOLINE

The substrate 1 of cytosolic phospholipase A(2) (cPLA(2)) is an ether- type thiophospholipid with arachidonic acid at the C-2 position and is required for the chromogenic assay for reliable and convenient high t hroughput screening. The original method of synthesis of 1 has signifi cant problems, resulting in extremely low overall yield and purity. We developed a novel and highly practical method of preparing sufficient quantities of pure 1 for assay. Our synthetic sequence is started wit h commercially available 1,2-O-isopropylidene-sn-grycerol (5) and is b ased on the following key steps: trityl migration reaction of 10 with boron trifluoride etherate to form 13, phosphocholine-forming reaction of 13 to yield 15, and efficient conversion of 15 into 1 by deprotect ion of a trityl group and condensation with arachidonic acid. Our meth od offers a practical means of large-scale production of 1 with excell ent high chemical purity, because of the introduction of arachidonic a cid at the last step of the synthetic sequence.