First asymmetric synthesis of 6-hydroxy-4-sphingenine-containing ceramides. Use of chiral propargylic alcohols to prepare a lipid found in human skin.
6-Hydroxy-(4E)-sphingenine-containing ceramides were found recently in human skin. We present here the first synthesis of the 6S and 6R diastereoisomers 2 and 3, which represent analogues of (2S,3R)-ceramide (1) having two allylic hydroxyl groups. Chiral propargylic alcohols 8 and 11, which were prepared by asymmetric dihydroxylation of alpha,beta-unsaturated ester 13 and allylic chloride 22, respectively, were employed as precursors of 2 and 3. Nucleophilic addition of lithiated TBS-protected propargylic ethers 25 and 32 to l-serine-derived aldehyde 26, respectively, afforded oxazolidine intermediates 27 and 33. Acid-mediated deprotection of the oxazolidine, followed by N-acylation and Birch reduction, completed the syntheses of 2 and 3.
Chun
Jiong
J
Department of Chemistry and Biochemistry, Queens College of The City University of New York, Flushing 11367-1597, USA.
Byun
Hoe-Sup
HS
Bittman
Robert
R
D002384:Catalysis; D002518:Ceramides / Q000138:chemical synthesis*; D004817:Epidermis / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013237:Stereoisomerism
C092210:6-hydroxy-4-sphingenine; D002518:Ceramides; D013110:Sphingosine