Synthesis of enantiomerically pure (Z)-(2′R)-1-O-(2′-methoxyhexadec-4′-enyl)-sn-glycerol present in the liver oil of cartilaginous fish

Synthesis of enantiopure (Z)-(2′R)-1-O-(2′-methoxyhexadec-4′-enyl)-sn-glycerol 1, the principal methoxylated glyceryl ether found in Nature, is described by a highly convergent five-step process taking place in 27% overall yield. The synthesis is based on an ether bond formation between the chiral synthon (R)-2,3-O-isopropylidene-sn-glycerol and (Z)-(R)-1-chlorohexadec-4-en-2-ol employing ground potassium hydroxide and tetra-n-butylammonium bromide as a catalyst under solvent free conditions.

Figure optionsDownload as PowerPoint slide

(R)-1-Chlorohexadec-4-yn-2-olC16H29ClOEe = 98%[α]D20=-12.2 (c 2.50, EtOH)Source of chirality: (R)-epichlorohydrin (98% ee)Absolute configuration: (R)

(Z)-(R)-1-Chlorohexadec-4-en-2-olC16H31ClOEe = 98%[α]D20=+2.0 (c 1.00, EtOH)Source of chirality: (R)-epichlorohydrin (98% ee)Absolute configuration: (R)

(Z)-(2′R)-1-O-(2′-Hydroxyhexadec-4′-enyl)-2,3-O-isopropylidene-sn-glycerolC22H42O4[α]D20=-5.7 (c 0.86, EtOH)Source of chirality: (R)-epichlorohydrin (98% ee) and (R)-solketal (99% ee)Absolute configuration: (2R,2′R)

(Z)-(2′R)-1-O-(2′-Methoxyhexadec-4′-enyl)-2,3-O-isopropylidene-sn-glycerolC23H44O4[α]D20=-13.1 (c 0.83, EtOH)Source of chirality: (R)-epichlorohydrin (98% ee) and (R)-solketal (99% ee)Absolute configuration: (2R,2′R)

(Z)-(2′R)-1-O-(2′-Methoxyhexadec-4′-enyl)-sn-glycerolC20H40O4[α]D20=-12.5 (c 0.84, CHCl3)Source of chirality: (R)-epichlorohydrin (98% ee) and (R)-solketal (99% ee)Absolute configuration: (2S,2′R)