The reaction of thiolates with 2,3-dibromo-1-propanol revisited: application to the synthesis of bis(fattyalkylthio)propanols

• Published in: Chemistry and physics of lipids 1999-09, Vol.101 (2), p.215-222
• Main Authors: Gernon, Michael D, Turcotte, Joseph G, Notter, Robert H, Wu, Min, Lear, Yvonne, Snelgrove, Jennifer L, Schwan, Adrian L
• Format: Article
• Language: English
• Subjects: Di-thio phospholipid analogs; Fattyalkylthio propanols; Lung surfactants; Magnetic Resonance Spectroscopy; Models, Chemical; Propanols - chemical synthesis; Propanols - metabolism; Sulfhydryl Compounds - metabolism
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/S0009-3084(99)00048-1

This work compares two reaction schemes for preparing 2,3-bis(fattyalkylthio)-1-propanols for further synthetic adaptation as hydrophobic analogs of lung surfactant phosphatidylcholines. An attempt to prepare 2,3-bis(fattyalkylthio)-1-propanols based on the previously published methods of Bell and co-workers (B.R. Ganong, C.R. Loomis, Y.A. Hannun, R.M. Bell, 1986. Proc. Natl. Acad. Sci. USA 83, 1184–1188; B.R. Ganong, R.M. Bell, 1987. Methods Enzymol. 141, 313–320; J.P. Walsh, L. Fahrner, R.M. Bell, 1990. J. Biol. Chem. 265, 4374–4381) was found to give the rearranged 1,3-bis(fattyalkylthio)-2-propanols as major products. As a reliable alternative, the reaction of ethyl 2,3-dibromopropionate with 2 equivalents of long chain sodium n-alkanethioates gave the corresponding ethyl 2,3-bis( n-alkylthio)propionates, which were then reduced with LiAlH 4 to yield the desired 2,3-bis(fattyalkylthio)-1-propanols. Both 13C and 1H NMR spectroscopy were used to differentiate the two possible 1,3- and 2,3-dithio substituted alcohol products and to rigorously assign their structures.