Hoe-Sup Byun

Synthesis of Immunostimulatory α-C-Galactosylceramide Glycolipids via Sonogashira Coupling, Asymmetric Epoxidation, and Trichloroacetimidate-Mediated Epoxide Opening

Stereocontrolled syntheses of alpha-C-GalCer (2) and its alpha-C-acetylenic analogue 6 were accomplished in high efficiency by a convergent construction strategy from 1-hexadecene and d-galactose. The key transformations include Sonogashira coupling, Sharpless asymmetric epoxidation, and Et(2)AlCl-catalyzed cyclization of an epoxytrichloroacetimidate to generate protected dihydrooxazine 21.

Asymmetric Synthesis of d-ribo-Phytosphingosine from 1-Tetradecyne and (4-Methoxyphenoxy)acetaldehyde

An asymmetric synthesis of d-ribo-phytosphingosine (1) was achieved by utilizing the ProPhenol (12)-catalyzed alkynylation of unsaturated aldehyde 8 to afford allylic propargylic alcohol (S)-6 followed by asymmetric epoxidation and opening of propargylic epoxy alcohol anti-5 with NaN(3)/NH(4)Cl. Deprotection and reduction of the resulting acyclic azide 3 then gave 1. Alkyne-azide 3 was subjected to an intramolecular click reaction, generating a bicyclic triazole, which was found to have unexpected vicinal coupling constants. Application of the advanced Mosher method verified the configurations of the three contiguous stereogenic centers of 1. An alkynyl azide analogue of 1, which may be useful as a glycosyl acceptor in the synthesis of alpha-galactosylceramide derivatives, was also readily prepared by this route.

Selective deuterium labeling of the sphingoid backbone: facile syntheses of 3,4,5-trideuterio-d-erythro-sphingosine and 3-deuterio-d-erythro-sphingomyelin.

Deuteration at C-4 and C-5 of sphingosine was achieved via a hydrogen-deuterium exchange reaction of a β-ketophosphonate intermediate catalyzed by ND₄Cl in D₂O/tetrahydrofuran. To install deuterium at C-3 of sphingosine and sphingomyelin, sodium borodeuteride reduction/cerium(III) chloride reduction of an α,β-enone in perdeuteromethanol was used.

Stereospecific and regiospecific ring opening of glycidol with primary and secondary alcohols mediated by diisobutylaluminium hydride

Regiospecific ring opening of (R)-(+)- or (S)-(–)-glycidol 1a, b with primary and secondary alcohols in the presence of diisobutylaluminium hydride provides 1-O-alkyl-sn-glycerol 2 without formation of the undesired regioisomer, 2-O-alkylglycerol 3. The configuration of the glycidol is preserved in the product.