Total synthesis of chain-length-uniform dolichyl phosphates and their fitness to accept hexoses in the enzymatic formation of lipoglycans.
Dolichols of defined uniform chain length (C35, C45, and C55) and geometry were prepared by total synthesis according to the following principle: (E,E)-Farnesol, activated as its 4-tolyl sulfone, is condensed with 8-chloroneryl benzyl ether, the sulfonyl group removed and the ether linkage cleaved by lithium/triethylamine. The resulting elongated prenol is converted again to its corresponding 4-toly/sulfone; at this stage isomers are removed by chromatography. After several cycles of this C10-elongation sequence the synthesis is completed in the same way but using 8-chlorocitronellyl benzyl ether as building block to introduce the saturated alpha-isoprene unit. The dolichols obtained were chemically phosphorylated (POCl3/Et3N). Both, the alcohols and their phosphate esters, are characterized spectroscopically. 1H- and 13C-NMR data are recorded for qualitative and stereochemical comparison with natural dolichols. The authentic dolichyl phosphates (Dol-7-P, Dol-9-P, and Dol-11-P) were assayed relative to the natural dolichyl phosphate mixture from pig liver as acceptors for transglycosylation from nucleoside diphosphate sugars (glucose, mannose) by standardized membrane vesicle preparations from plants (Volvox) and animals (liver). Even the shortest chain dolichyl 7-phosphate has full activity in this lipoglycan-forming reaction.
D055598:Chemical Phenomena; D002621:Chemistry; D004288:Dolichol Phosphates / Q000138:chemical synthesis*; D006601:Hexoses / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis*
D004288:Dolichol Phosphates; D006601:Hexoses; D008070:Lipopolysaccharides; D011106:Polyisoprenyl Phosphates