D-Mannosamine hydrochloride

D-Mannosamine hydrochloride (2-amino-2-deoxy-D-mannose hydrochloride): ionic hydrogen bonding in saccharides involving chloride and aminium ions.[Pubmed:35380125]

Acta Crystallogr C Struct Chem. 2022 Apr 1;78(Pt 4):223-230.

D-Mannosamine hydrochloride (2-amino-2-deoxy-D-mannose hydrochloride), C(6)H(14)NO(5)(+).Cl(-), (I), crystallized from a methanol/ethyl acetate/n-hexane solvent mixture at room temperature in a (4)C(1) chair conformation that is slightly distorted towards the (C3,O5)B form. A comparison of the structural parameters of (I) with the corresponding parameters in alpha-D-glucosamine hydrochloride, (II), and beta-D-galactosamine hydrochloride, (III)/(III'), was undertaken to evaluate the effects of ionic hydrogen bonding on structural properties. Three types of ionic hydrogen bonds are present in the crystals of (I)-(III)/(III'), i.e. N(+)-H...O, N(+)-H...Cl(-), and O-H...Cl(-). The exocyclic structural parameters in (I), (II), and (III)/(III') appear to be most influenced by this bonding, especially the exocyclic hydroxy groups, which adopt eclipsed conformations enabled by ionic hydrogen bonding to the chloride anion. Anomeric disorder was observed in crystals of (I), with an alpha:beta ratio of 37:63. However, anomeric configuration appears to exert minimal structural effects; that is, bond lengths, bond angles, and torsion angles are essentially identical in both anomers. The observed disorder at the anomeric C atom of (I) appears to be caused by the presence of the chloride anion and atom O3 or O4 in proximal voids, which provide opportunities for hydrogen bonding to atom O1 in both axial and equatorial orientations.

Synthesis of non-natural ManNAc analogs for the expression of thiols on cell-surface sialic acids.[Pubmed:17406481]

Nat Protoc. 2006;1(5):2377-85.

The sialic acid biosynthetic pathway in mammalian cells utilizes N-acetyl-D-mannosamine (ManNAc) as a natural metabolic precursor and has the remarkable ability to biosynthetically process non-natural ManNAc analogs. Herein, we describe a recipe-style protocol for the synthesis of the novel peracetylated analog Ac5ManNTGc (1) that contains a pendant acetylthio- group and enables incorporation of thiol functionalities into the glycocalyx of living cells. We also describe the synthesis of the oxygen analog Ac5ManNGc (2), which serves as an appropriate control compound for biological experiments with 1. Both 1 and 2 were prepared from a reported, common intermediate 8, which is selectively acetylated at the hydroxyl groups. In contrast to previous methods, this synthetic approach introduces O-acetyl groups first, followed by N-acylation. Starting from the commercially available D-Mannosamine hydrochloride (5), gram quantities of both 1 and 2 can be prepared over five steps in about 2-3 weeks.

Synthesis and high-throughput screening of N-acetyl-beta-hexosaminidase inhibitor libraries targeting osteoarthritis.[Pubmed:15357586]

J Org Chem. 2004 Sep 17;69(19):6273-83.

C1 Nitrogen iminocyclitols are potent inhibitors of N-acetyl-beta-hexosaminidases. Given hexosaminidases' important roles in osteoarthritis, we developed two straightforward and efficient syntheses of C1 nitrogen iminocyclitols from two readily available starting materials, D-Mannosamine hydrochloride and the microbial oxidation product of fructose. A diversity-oriented synthetic strategy was then performed by coupling these core structures with various aldehydes, carboxylic acids, and alkynes to generate three separate libraries. High-throughput screening of the generated libraries with human N-acetyl-beta-hexosaminidases produced only moderate inhibitory activities. However, the synthetic approach and screening strategy for these compounds will be applied to develop new potent inhibitors of human N-acetyl-beta-hexosaminidases, particularly when combined with the structural information of these enzymes.

Chirospecific synthesis of D and Lp-chlorohomophenylalanine N-t-BOC DCHA salts.[Pubmed:24190745]

Amino Acids. 1994 Feb;6(1):97-105.

The chirospecific conversions of D-glucosamine hydrochloride and D-Mannosamine hydrochloride to the configurationally stable L and D isomers of N-t-butyloxycarbonylserinal were carried out byt-butylcarbonylation followed by sodium borohydride reduction and sodium meta-periodate oxidation. Reaction of the L and D aldehydes with the Wittig reagent prepared from 4-chlorobenzyltriphenylphosphonium chloride and butyl lithium followed by catalytic hydrogenation, Jones oxidation and salt formation with dicyclohexylamine gave the DCHA salts of the D and L isomers ofp-chlorohomophenylalanine N-t-Boc in high enatiomeric excess. The optical purity of the title compounds was established by hydrolysis to the respective free amino acids, followed by chiral derivatization and HPLC analysis.

Haloacetamido analogues of 2-amino-2-deoxy-D-mannose. Syntheses and effects on tumor-bearing mice.[Pubmed:7277392]

J Med Chem. 1981 Jul;24(7):848-52.

Haloacetamido analogues (fluoro, chloro, and bromo) of 2-deoxy-2acetamido-D-mannose and their tetra-O-acetates were prepared from D-Mannosamine hydrochloride, with either chloroacetic or bromoacetic anhydride or by dicyclohexylcarbodiimide-activated condensation with fluoroacetate followed by acetylation. Comparative specific rotations and 13C and 1H NMR spectra were consistent with a beta configuration for the tetra-O-acetylated derivatives, 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-(bromoacetamido)-beta-D-mannose and the corresponding analogue of glucose inhibited [3H]thymidine incorporation into mouse L1210 leukemia cells by 50% (IC50) at concentrations between 6 and 9 microM. 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-(chloroacetamido)-beta-D-mannose was 3-fold more active in the thymidine-incorporation assay (143 +/- 24 microM, IC50) than was the corresponding analogue in the glucose series (425 +/- 62 microM; p = 0.05). All of the haloacetamido free sugars, as well as the tetra-O-acetates of the fluoroacetamido analogues in the glucose, galactose, and mannose series, were inactive in the thymidine incorporation assay at 1mM. In the mannose series the tetra-O-acetylated chloroacetamido and bromoacetamido analogues, as well as the bromoacetamido free sugar, could be administered at relatively high in vivo tolerated doses compared to the corresponding analogues in the galactose and glucose series. These three mannose analogues produced high proportions of cures of Ehrlich tumor-bearing B6D2F1 mice, whereas in the galactose and glucose series only the tetra-O-acetylated bromoacetamido analogues had previously produced in vivo chemotherapeutic activity.