Journal of Organic Chemistry 2003-12-26

Synthesis and supramolecular properties of conformationally restricted and flexible phospholipids.

Lauri Vares, Atanas V Koulov, Bradley D Smith

Index: J. Org. Chem. 68(26) , 10073-8, (2003)

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Abstract

Short synthetic routes are described to produce structurally related phospholipids that are either conformationally restricted or flexible. The conformationally restricted structures have a cyclopropyl ring in the interfacial region of the phospholipid. The key synthetic step is a cyclopropanation reaction between 2(5H)-furanone and a stabilized chloroallylic phosphonate anion. The synthetic routes enable the incorporation of different polar headgroups as well as nonpolar tails at late stages in the sequence. The phosphoethanolamine derivatives 1b and 2b readily form encapsulating vesicles, however, dye leakage from vesicles composed of the restricted phospholipid 1b is significantly slower than from vesicles composed of flexible analogue 2b. Physicochemical analyses using 31P NMR, differential scanning calorimetry, fluorescence anisotropy, and Langmuir-Blodgett films suggest that the decreased permeability of membranes composed of conformationally restricted 1b is due to its ability to pack more closely in a bilayer assembly.