Stereoselective synthesis of beta-1-C-substituted 1,4-dideoxy-1,4-imino-D-galactitols and evaluation as UDP-galactopyranose mutase inhibitors.

The synthesis of 1-C-substituted 1,4-dideoxy-1,4-imino-D-galactitols involving nitrone umpolung is described. The SmI(2)-induced key coupling proved highly stereoselective in favor of the beta-C-substituted products bearing a three-carbon chain at the pseudoanomeric position. Pyrrolidines 9 and 10, as well as the bicyclic compounds 8 and 11, exhibit weak inhibition of the activity of the UDP-galactopyranose mutase from Escherichia coli.

Stereoselective synthesis of alpha-C-Substituted 1,4-dideoxy-1,4-imino-D-galactitols. Toward original UDP-Galf mimics via cross-metathesis.

[reaction: see text] Various alpha-C-substituted 1,4-dideoxy-1,4-imino-d-galactitols were prepared efficiently from 1-O-acetyl-2,3,5,6-tetra-O-benzyl-d-glucofuranose by a four-step sequence involving as the key step the highly syn-selective TMSOTf-catalyzed addition of silylated nucleophiles to a glycofuranosylamine. Cross-metathesis of the alpha-C-allylated iminogalactofuranose derivative with an original uridin-5'-yl vinylphosphonate led to novel UDP-galactofuranose mimics. Such compounds are of interest as potential inhibitors of the mycobacterial galactan biosynthesis pathway.

New derivatives of D-mannaric and galactaric acids. Synthesis of a new stereoregular Nylon 66 analog from carbohydrate-based monomers having the D-manno configuration.

2,3,4,5-Tetra-O-methyl-D-mannaric and galactaric acids and their bis(pentachlorophenyl) esters have been prepared as crystalline compounds, in good yields, from D-mannitol and galactitol, respectively. A new stereoregular polyamide, analogous to Nylon 66, has been prepared by polycondensation of bis(pentachlorophenyl) 2,3,4,5-tetra-O-methyl-D-mannarate with 1,6-diamino-1,6-dideoxy-2,3,4,5-tetra-O-methyl-D-mannitol dihydrochloride. The polymer has a M(w) of 31,100 with a polydispersity of 1.5 (GPC). It was highly hygroscopic and soluble in ethanol, acetone, dimethyl sulfoxide, N,N-dimethylformamide and chloroform, but only slightly soluble in water.

Authentic standards for the reductive-cleavage method. The positional isomers of partially methylated and acetylated or benzoylated 1,5-anhydro-D-galactitol.

Described herein is an efficient method for the synthesis of the sixteen positional isomers of methylated and acetylated or benzoylated 1,5-anhydro-D-galactitol. The compounds are generated simultaneously by partial methylation of 1,5-anhydro-D-galactitol and subsequent benzoylation, and the individual isomers are obtained in pure form by high-performance liquid chromatography. Debenzoylation and acetylation yielded the desired acetates. Reported herein are the 1H NMR spectra of the benzoates and the electron-ionization mass spectra of the acetates and the tetra-O-methyl derivative. Also reported for the acetates and the tetra-O-methyl derivative are their linear temperature-programmed gas-liquid chromatography retention indices on three different capillary columns.

[Synthesis of 2-acetamido-1,4-imino-1,2,4-tridesoxy-D-galactitol and competitive inhibition of human lysosomal beta-hexosaminidase A]. / Synthese von 2-Acetamido-1,4-imino-1,2,4-tridesoxy-D-galaktitol und kompetitive Inhibition der humanen lysosomalen beta-Hexosaminidase A.

The synthesis of 2-acetamido-1,4-imino-1,2,4-trideoxy-D-galactitol (1; 2-acetamido-4-amino-1,4-anhydro-2,4-dideoxy-D-galactitol) by two different routes starting from 2-acetamido-2-deoxy-D-glucose is described. Compound 1 is a competitive inhibitor of human lysosomal beta-hexosaminidase A with K(i) values of 18 microM (beta-subunit) and 220 microM (alpha-subunit). Similar properties were found for the already known 2-acetamido-2-deoxy-D-gluco-hydroximo-1,4-lactone.

Derivatives of 2,3-anhydro-DL-threitol, 2,3-anhydroerythritol, 2,3:4,5-dianhydrogalactitol, and 2,3:4,5-dianhydroallitol.

alpha, omega-Disubstituted derivatives of 2,3-anhydro-DL-threitol (2), 2,3-anhydroerythritol (4), 2,3:4,5-dianhydrogalactitol (8), and 2,3:4,5-dianhydroallitol (12) have been synthesised by epoxidation of the appropriate alkeness and dienes. Benzyloxy carbonyl groups were used for protecting the primary hydroxyl groups during epoxidation.