Facile synthesis of plasmalogens via Barbier-type reactions of vinyl dioxanes and vinyl dioxolanes with alkyl halides in LiDBB solution.
Plasmalogens (i.e. plasmenylcholines or plasmenylethanolamines) are a biologically important class of glycerophospholipids that have been difficult to synthesize due to the presence of an acid and oxidatively labile (Z)-vinyl ether substituent at the sn-1 position and a base-labile sn-2 acyl substituent that easily migrates during silica gel purification. We report two facile synthetic methods for the preparation of racemic plasmenylcholines via a tandem reductive vinyl dioxane/dioxolane ring opening and alkyliodide coupling process that proceeds in a single pot reaction. The key step in the formation of (Z)-vinyl ether precursors for the production of plasmenylcholines is accomplished using LiDBB under Barbier-type conditions to give the corresponding TBDMS-protected 1-O-Z'-vinylglycerol intermediate in moderate yields. This pathway is the most direct synthetic route for the formation of plasmenylcholines to date, requiring a total of six transformations from acrolein and glycerol or solketal as inexpensive starting materials, to generate glycerophosphocholine-type plasmalogens in 4% overall yield.
Shin
Junhwa
J
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-1393, USA.
Gerasimov
Oleg
O
Thompson
David H
DH
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D004146:Dioxanes / Q000737:chemistry*; D004148:Dioxolanes / Q000737:chemistry*; D005990:Glycerol / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010955:Plasmalogens / Q000138:chemical synthesis*; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000737:chemistry*
D004146:Dioxanes; D004148:Dioxolanes; D010955:Plasmalogens; D014753:Vinyl Compounds; C032459:choline plasmalogens; D005990:Glycerol