Synthetic Approaches to Novel Archaeal Tetraether Glycolipid Analogues<sup>†</sup>

Symmetrical and unsymmetrical archaeal tetraether glycolipid analogues have been prepared. The syntheses are based upon the elaboration of lipid cores from versatile chiral starting materials followed by simultaneous or sequential introduction of polar headgroups. Three pathways (A−C) were elaborated for the synthesis of stereochemically defined lipids <b>14</b>−<b>16</b> characterized by a straight bridging spacer and two dihydrocitronellyl chains attached to glycerol units at the <i>sn</i>-3 and <i>sn</i>-2 positions, respectively. Pathway C appeared to be particularly advantageous for the synthesis of tetraether <b>9</b>, which possesses a cyclopentane unit as found in thermoacidophilic lipids. Diglycosylated lipids <b>4</b>−<b>6</b> were produced in 49−53% yields by reaction of diols <b>14</b>−<b>16</b> with β-d-galactofuranosyl donor <b>31</b>, whereas unsymmetrical lipids possessing either two different carbohydrate units <b>7</b> or a saccharidic moiety and a phosphate group <b>8</b> were efficiently prepared from monoprotected diol <b>35</b>. These compounds represent the first examples of tetraether-type analogues containing a phosphate unit and/or glycosyl moieties.