Novel chemistry of amino sugars: Pathway to glycosphingolipids and glycopeptides

Novel chemistry of 2-aminosugars has been investigated and the findings provided an efficient pathway to prepare biologically interesting glycosphingolipids and glycopeptides for immunochemical studies.;The above approach was extended to the concise and large-scale synthesis of important and expensive 2-acetamido-2-deoxy-beta-D-hexopyranosides. By suitable manipulation at the 3-position of the furanose oxazoline, three methyl 2-acetamido-2-deoxy-beta-D-hexopyranosides (galacto, allo- and gulo-) and two methyl 2-acetamido-2,4,6-deoxy-2,4-diamino-beta-D-hexopyranosides (galacto- and gulo-) were readily prepared via short sequences. Meanwhile, a biologically important muramic acid and a repeating beta-D-GlcNAc (1→34)-beta-D-MurNAc disaccharide unit of bacterial cell wall peptidoglycan were also synthesized from the furanose oxazoline. Both can be readily coupled with suitable peptides to afford muramylpeptides for use as immunoadjuvants and bacterial cell wall biosynthetic precursors.;Based on these new findings, a novel and flexible synthetic approach to C-18-phytosphingosine was developed via the key reactions of zinc-mediated reductive fragmentation and olefin cross metathesis (OCM). Using this approach, two kinds of unsaturated and saturated D-xylo and natural D-ribo-phytosphingosines were conveniently synthesized from the corresponding 2-acetamido-2-deoxy-beta-D-hexopyranosides. Another efficient approach to sphingolipids including truncated sphingosine, sphinganines and phytosphingosines was also explored by asymmetric aldol condensations using a chiral auxiliary.;Following these sphingolipid syntheses, the potent immunostimulant alpha-galactosylceramide (KRN7000) was successfully prepared by an OCM strategy in optimal and convergent routes. Improved glycosylation yields and excellent alpha-selectivity could be obtained with tetrabenzyl galactopyranosyl iodide donor and a truncated C-6-phytosphingosine acceptor. The truncated aglycon moiety was smoothly extended by OCM reactions in high yields. The OCM strategy was further applied to the synthesis of beta-lactosylceramide, a common core structure of many glycosphingolipids (GSLs). The successful application of OCM in GSL synthesis provides us with a general and flexible route for rapid access to their analogues and derivatives.;A new and direct approach leading to 2-acetamido-2-deoxy-beta-D-glucopyranosides has been developed via a reactive furanose oxazoline. A variety of unprotected 2-acetamido-2-deoxy-beta-D-glucopyranosides have been synthesized in just two steps from abundant D-GlcNAc. Glycosidation of alcohols is mild, highly stereoselective and compatible with a range of functional groups. The easy and large-scale preparation of the furanose oxazoline donor from D-GlcNAc allowed the synthesis of 2-acetamido-2-deoxy-beta-D-glucopyranosides in a simple and practical manner.