Asymmetric syntheses of new analogues of ceramide

This dissertation presents the asymmetric total syntheses of natural occurring ceramides and analogues bearing modifications in the sphingoid backbone. Also included in this dissertation is a novel methodology for the preparation of chiral propargylic alcohols.; Chapter 1 presents the syntheses of ceramide analogues in which the trans double bond of natural occurring ceramide is incorporated a benzene or pyridine ring. Two efficient and stereoselective routes are described. The first route involves the addition of an aryllithium or a heteroaryllithium reagent to an L-serine-derived aldehyde, followed by hydrolysis of the oxazolidine, liberation of the amino group, and N-acylation. The second route utilizes a Heck reaction to afford an (E)-α,β-unsaturated ester, then Sharpless asymmetric dihydroxylation for the construction of the desired chirality.; Chapter 2 presents a simple and convenient method for the regiospecific introduction of unsaturation (both as a single trans double bond and as a conjugated diene) into the sphingoid backbone of ceramide by employing organosulfur chemistry. C-Alkylation of a β-ketosulfoxide and elimination of PhS(O)H provided a conjugated ketone.; Chapter 3 presents the synthesis of a new analogue of ceramide with deuterium in the sphingoid backbone for quantification of sphingosine 1-phosphate in biological samples by stable isotope dilution mass spectrometry. Addition of lithium pentadecyne-d₂₇ to Garner aldehyde in the presence of HMPA resulted in high erythro selectivity.; Chapter 4 presents the first synthesis of the 5R and 5S diastereoisomers of the N-acyl derivatives of 5-hydroxy-3-sphingosine, which represent regioisomers of natural occurring 2S,3R-ceramide. The key steps include the synthesis of α,β-unsaturated ketone intermediates from N-Cbz- and N-Boc-L-serine and diastereoselective reduction of the enones.; Chapter 5 presents the first synthesis of the 6S and 6R diastereoisomers of 6-hydroxy-4-sphingenine-containing ceramides, which were found recently in human skin. Chiral propargylic alcohols were prepared via Sharpless asymmetric dihydroxylation of an α,β-unsaturated ester and allylic chloride.; Chapter 6 presents a simple and efficient method for the preparation of chiral propargylic alcohols which are important chiral building blocks for the synthesis of natural and unnatural products.; Chapter 7 presents the syntheses of ceramide analogues in which the trans double bound of naturally occurring ceramide was changed to an allene. (Abstract shortened by UMI.)...