TY - JOUR
T1 - Asymmetric Synthesis of Methoxylated Ether Lipids
T2 - Total Synthesis of n-3 Polyunsaturated Docosahexaenoic Acid-Like Methoxylated Ether Lipid
AU - Sigurjónsson, Svanur
AU - Lúthersson, Einar
AU - Magnússon, Carlos D.
AU - Gudmundsson, Haraldur G.
AU - Das, Erika
AU - Haraldsson, Gudmundur G.
N1 - Funding Information: This work was funded by the Icelandic Research Fund (100030─021-023; 120023─021-023; and 141595─051-053) that is also acknowledged for a doctorate student grant (SS) (174396─051-053). Dr. Sigrídur Jónsdóttir University of Iceland is acknowledged for NMR and accurate MS measurements. Dr. Iren Stoknes and Dr. Geir Frode at EPAX AS in Ålesund, Norway, and Dr. Elin Kulås and Dr. Erling Odden at BASF AS in Sandefjord, Norway, are acknowledged for GLC analysis. Publisher Copyright: © 2022 American Chemical Society. All rights reserved.
PY - 2022/10/24
Y1 - 2022/10/24
N2 - The first total synthesis of a docosahexaenoic acid (DHA)-like methoxylated ether lipid (MEL) is reported. This compound constitutes an all-cis methylene skipped hexaene framework identical to that present in DHA, the well-known omega-3 polyunsaturated fatty acid. The polyene C22 hydrocarbon chain, bearing a methoxyl group in the 2-position and R-configuration at the resulting chiral center, is attached by an ether linkage to the pro-S hydroxymethyl group (sn-1 position) of a glycerol backbone. The asymmetric synthesis is highly convergent and based on the polyacetylene approach involving iterative copper-promoted coupling reactions of propargyl bromides with terminal alkynes and semihydrogenation of the resulting hexayne. Starting from enantiopure R-solketal and racemic epichlorohydrin, the targeted MEL was accomplished in an 8.2% yield over eight steps (longest linear sequence) involving an enantio- and diastereopure glyceryl glycidyl ether key C6-building blocks from which the polyynes were constructed.
AB - The first total synthesis of a docosahexaenoic acid (DHA)-like methoxylated ether lipid (MEL) is reported. This compound constitutes an all-cis methylene skipped hexaene framework identical to that present in DHA, the well-known omega-3 polyunsaturated fatty acid. The polyene C22 hydrocarbon chain, bearing a methoxyl group in the 2-position and R-configuration at the resulting chiral center, is attached by an ether linkage to the pro-S hydroxymethyl group (sn-1 position) of a glycerol backbone. The asymmetric synthesis is highly convergent and based on the polyacetylene approach involving iterative copper-promoted coupling reactions of propargyl bromides with terminal alkynes and semihydrogenation of the resulting hexayne. Starting from enantiopure R-solketal and racemic epichlorohydrin, the targeted MEL was accomplished in an 8.2% yield over eight steps (longest linear sequence) involving an enantio- and diastereopure glyceryl glycidyl ether key C6-building blocks from which the polyynes were constructed.
UR - https://www.scopus.com/pages/publications/85141024887
U2 - 10.1021/acs.joc.2c01991
DO - 10.1021/acs.joc.2c01991
M3 - Article
SN - 0022-3263
VL - 87
SP - 14623
EP - 14635
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 21
ER -