Synthesis of ceramide analogues having the C(4)-C(5) bond of the long-chain base as part of an aromatic or heteroaromatic system.
Two efficient and stereoselective methods are described for the preparation of aryl and heteroaryl ceramide analogues 2 and 3. The first route involves the addition of an aryllithium or a heteroaryllithium reagent (7a or 25a, respectively) to the L-serine-derived aldehyde 4, followed by hydrolysis of the oxazolidine, liberation of the amino group, and N-acylation. The second route, which was used to prepare arylceramide analogue 2 in eight steps and 28% overall yield starting with 3-bromobenzaldehyde, utilizes a Heck reaction to afford (E)-alpha,beta-unsaturated ester 16, then osmium-catalyzed asymmetric dihydroxylation for the introduction of the desired chirality at C-2 and C-3. Regioselective alpha-azidation of alpha-O-nosyl-beta-hydroxyester 18 with sodium azide, followed by LiAlH(4) reduction of the azido and ester groups and N-acylation, complete the synthesis of arylceramide analogue 2.
Chun
J
J
Department of Chemistry and Biochemistry, Queens College of The City University of New York, Flushing, New York 11367-1597, USA.
He
L
L
Byun
H S
HS
Bittman
R
R
D001555:Benzene Derivatives / Q000138:chemical synthesis*; D002518:Ceramides / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D008566:Membranes / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis*; D012672:Semliki forest virus / Q000737:chemistry; D013237:Stereoisomerism
D001555:Benzene Derivatives; D002518:Ceramides; D007202:Indicators and Reagents; D011725:Pyridines