A new reagent for the removal of the 4-methoxybenzyl ether: application to the synthesis of unusual macrocyclic and bolaform phosphatidylcholines

• Published in: Journal of organic chemistry Vol. 57; no. 6; pp. 1777 - 1783
• Main Authors: Hebert, Normand, Beck, Alain, Lennox, R. Bruce, Just, George
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.03.1992; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Lipids; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; PHOSPHITE-TRIESTER APPROACH; ANALOG; DEOXYNUCLEOSIDE PHOSPHORAMIDITES; BONDS; EFFICIENT SYNTHESIS; MEMBRANES; PHOSPHOLIPIDS; CLEAVAGE; ACID BROMOALKYL ESTERS; Protecting group; Acetylenic compound; Aliphatic compound; Phospholipid; Lactone; Review; Oxygen heterocycle; Complex lipid; Fatty acids; Oxidative coupling; Phosphorus Organic compounds; Macrocycle; Alditol; Phosphatidylcholine; Diynic compound; Acylation
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00032a033

The total synthesis of two novel polymerizable phosphatidylcholines has been accomplished using 3-(4-methoxybenzyl)-sn-glycerol 10 as starting material. Diacylation of 10 with 13-tetradecynoic acid followed by oxidative coupling of the alkynes gives the 32-membered glycerol macrocycle 17. Sequential acylation of 10 with palmitic acid and 15-hexadecynoic acid followed by oxidative coupling gives the bolaform 16, tethered at the 2-position of the glycerol. A new method for the cleavage of 4-methoxybenzyl ethers using dimethylboron bromide at -78-degrees-C in dichloromethane is described. 1,3-Diacetylenes, 1,4-dienes, and esters are stable under the experimental conditions, and the migration of acyl chains from secondary to primary positions is totally suppressed. The diacylglycerols are then efficiently converted into the corresponding phosphatidylcholines by tetrazole-catalyzed phosphitylation with 2-cyanoethyl 2-bromoethyl N,N-diisopropylamino phosphite, oxidation, and treatment with trimethylamine to simultaneously displace the bromide and eliminate the cyanoethyl group.