Improved process for the preparation of oxidized phospholipids

摘要

603980 The disclosure relates to a process for the preparation of 1-hexadecyl-2-(4’-carboxy)butylglycerol and 1-hexadecyl-2-(4’-carboxy)butyl-glycero-3-phosphocholine compounds which comprises: reacting a first compound having a glycerolic backbone, wherein a hydroxyl group at position sn-3 of the glycerolic backbone is protected with a trityl group, with a second compound having an unsaturated bond and having the formula Br(CH2)4CHCH2, to obtain a third compound. providing the solution of said third compound, removing insoluble impurities from said solution to obtain a purified third compound. reacting said purified third compound with a mixture of periodate and permanganate to form an intermediate compound. removing said trityl group thereby forming said 1-hexadecyl-2-(4’-carboxy)butyl-glycerol Isolating the resulting compound through phase separation. Where 1-hexadecyl-2-(4’-carboxy)butyl-glycero-3-phosphocholine is to be prepared the process further comprises: reacting the isolated 1-hexadecyl-2-(4’-carboxy)butyl-glycerol via a methyl ester compound with POCl3, thereby forming the compound having a reactive phosphorous containing group attached to the glycerolic backbone, and converting the reactive phosphorous-containing group to a phosphorus containing moiety to form a compound incorporating a phosphocholine moiety, hydrolyzing said methyl ester moiety of said compound incorporating a phosphocholine moiety thereby forming said 1-hexadecyl-2-(4’-carboxy)butyl-glycero-3-phosphocholine. The solvent for step (ii) may be hexane, step (viii) may be achieved using Lithium Hydroxide(LiOH). Compounds and intermediates are also disclosed.