Glycal

About: Glycal is a research topic. Over the lifetime, 897 publications have been published within this topic receiving 17422 citations.

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose.

Abstract: The incorporation of basic substituents into the structurally conserved domains of cell wall lipopolysaccharides has been identified as a major mechanism contributing to antimicrobial resistance of Gram-negative pathogenic bacteria. Inhibition of the corresponding enzymatic steps, specifically the transfer of 4-amino-4-deoxy-ʟ-arabinose, would thus restore the activity of cationic antimicrobial peptides and several antimicrobial drugs. C-glycosidically-linked phospholipid derivatives of 4-amino-4-deoxy-ʟ-arabinose have been prepared as hydrolytically stable and chain-shortened analogues of the native undecaprenyl donor. The C-phosphonate unit was installed via a Wittig reaction of benzyl-protected 1,5-arabinonic acid lactone with the lithium salt of dimethyl methylphosphonate followed by an elimination step of the resulting hemiketal, leading to the corresponding exo- and endo-glycal derivatives. The ensuing selective monodemethylation and hydrogenolysis of the benzyl groups and reduction of the 4-azido group gave the α-ʟ-anomeric arabino- and ribo-configured methyl phosphonate esters. In addition, the monomethyl phosphonate glycal intermediates were converted into n-octyl derivatives followed by subsequent selective removal of the methyl phosphonate ester group and hydrogenation to give the octylphosphono derivatives. These intermediates will be of value for their future conversion into transition state analogues as well as for the introduction of various lipid extensions at the anomeric phosphonate moiety.

New Synthetic Pathways to C-Glycosides

Abstract: C-glycopyranosyl compounds exhibit antimicrobial, antifungal, and antitumor activities, most probably based on enzyme inhibition or interference with cell surface recognition phenomena. Recent developments in glycobiology have shown the importance of the glycoside component of glycoproteins for cell recognition and differentiation processes. C-glycosidic analogues of that component would be metabolically stable, and thus offer enhanced therapeutic value. Synthesis of a configurational variety of e.g. amino (glycopyranosyl) methanes is thus an important synthetic goal. The amino group would allow linking the C-glycoside to a variety of scaffolds. Our first approach has been to C-link a C-N synthon (HCN or CH 3 NO 2 ) to the anomeric carbon of a natural carbohydrate. We have realized this with cyanide on glycal, on per-O-acetyl sugars and on cyclic acetal protected glycosyl fluorides, prepared by a novel method. The catalytic hydrogenation of glycosyl cyanides presented challenges and new synthetic possibilities. With CH 3 NO 2 , and 4,6-O-alkylidene protected D-glucose or D-mannose derivatives, we obtained very good yields of cyclic Henry condensation products in THF with a novel catalytic procedure. The novel reduction of the resulting nitro (4,6-O-benzylidene-β-D-glycopyranosyl) methane with Fe 0 /Ni 0 in THF/H 2 O/CO 2 readily supplied amino (4,6-O-benzylidene-β-D--glucopyranosyl) methane, derivatives of which were diastereodiversified into D-allo, D-manno, and D-altro C-glycosides. These approaches fail, however, if prerequisite natural carbohydrate precursors are not available in a given case. Thus, a total synthesis scheme was also initiated. Phthalimido acetaldehyde diethylacetal and 4-penten-2-ol, with TiCl 4 , form 2-methyl-4-chloro-6-phthalimido-methyl tetrahydropyran, which was functionalized into phthalimido (6-deoxy-β-D,L-hexopyranosyl) methanes. Chiral extensions of this method are possible. C-'disaccharides' became available from the Ferrier 'dimerisation' of glycals, and from the hydrogenation of glycosyl cyanides.

Synthesis of β‐C‐galacto‐Pyranosides with Fluorine on the Pseudoanomeric Substituent.

Abstract: β-C-galacto-Pyranosides with CHF and CF2 substitutes for the glycosidic oxygen were prepared through a four-step sequence starting from a central 1-thio-1,2-O-isopropylidene acetal alcohol and different α-fluoro- and α,α-difluoro acids. The key step in the synthesis is the oxocarbenium cyclization of an intermediate enol ether-thioacetal to a C1-substituted glycal.

In(OTf)3 — A New Efficient Lewis Acid Catalyst for Stereoselective C-Glycosylation Reactions of Glycal Derivatives.

Abstract: A variety of glycal derivatives reacted smoothly with allyltrimethylsilane and trimethylsilylcyanide in neat condition as well as in dichloromethane in the presence of 2–5 mol% of In(OTf)3 affording the corresponding 2,3-unsaturated C-glycosides in excellent yields and moderate to excellent α-selectivities.