Chemical synthesis of 1- O-(D)- and 3- O-(L)-glyceryl monoethers, diethers and derivatives: Glycerides, monoester phospholipids and diether phospholipids

Abstract

1. 1. A convenient route to the synthesis of 1- O-glyceryl ether from 3- O-glyceryl ether is reported. This technique, which is based on the procedure of Lands and Zschocke 35 for conversion of 3- O-benzylglycerol to 1- O-benzylglycerol, utilized either 3- O-hexadecylglycerol or 3- O-octadecylglycerol as the starting material. The ether was converted to its ditosylate and this latter group was displaced with freshly fused potassium acetate in anhydrous ethanol. Alkaline hydrolysis yielded the desired 1- O-alkyl glycerol, with an equal but opposite optical rotation to the starting material, in good yields. 2. 2. 1- O- cis-9'-Octadecenyl-2- O-octadecanoylglycerol (2-stearoyl selachyl al-cohol) was synthesized by borate replacement of 1- O- cis-9'-octadecenyl-2- O-octade-canoyl-3- O-tritylglycerol in triethyl borate and boric acid, followed by column chromatography on neutral silicic acid. Catalytic amounts of HClO 4 isomerizes 2-stearoyl selachyl alcohol completely to its positional isomer 3-stearoyl selachyl alcohol. Acylation of 1- O-cis-9'-octadecenylglycerol in the presence of up to 2 M excess of acyl chloride, was found to occur preferentially at the primary hydroxyl group forming 3-stearoyl selachyl alcohol and the diacyl derivatives (dipalmitoyl, dioleoyl and distearoyl selachyl alcohol) formed in good yield only when a 4–6 M excess of acyl chloride was used. The properties of the synthetic diacyl-glyceryl derivatives correlated closely with the natural diacyl-glyceryl monoether isolated from dog fish liver oil. 3. 3. 1,2-Di- O- cis-9'-octadecenylglycerol which was synthesized by acid hydrolysis of its trityl derivative was converted to the corresponding phosphorylethanolamine and phosphorylcholine derivatives; 2- and 3-stearoyl selachyl alcohol were converted to their phosphoryl ethanolamine and phosphorylcholine derivatives. The physical properties of the monoethers, monoacyl monoethers, diethers and their corresponding phospholipids are tabulated and discussed. Comparable results in properties between the synthetic 1- O- cis-9'-octadecenyl-2- O-octadecanoyl-3-glycerophosphorylethanolamine and the natural monoether monoacyl glycerophosphorylethanolamine isolated from bovine erythrocytes were found.