First Total Synthesis of Two 1‐O‐Alkylglycerols Based Alkyne Analogues of Bioactive Natural Products

Abstract

Alkylglycerols (AKGs) with a straight-chain alkane or alkene are ether lipids abundant in the liver oil of some elasmobranch fish species such as ratfishes and some sharks. Natural shark liver oil (SLO) mixture displays several known biological activities and most of its identified alkylglycerols were also obtained individually in pure form by total synthesis. However, the synthesis of alkylglycerols containing at least one alkyne moiety in the alkyl chain has yet not been reported. In this work, we describe the first total synthesis of 1-O-alkylglycerols based alkyne (2S)-3-((4-methoxytridec-6-yn-1-yl)oxy)propane-1,2-diol ( 10) and (S)-3-(((R)-12-methoxyoctadec-9-yn-1-yl)oxy)propane-1,2-diol (11), analogues of bioactive ether lipids found in the SLO mixture. Oxiranes opening by alkynyl boranes and solketal etherification are the key steps with a global yield up to 72 % in eight steps sequence.