Fragmentation of deprotonated d-ribose and d-fructose in MALDI—Comparison with dissociative electron attachment

We present a detailed, collaborative study on the fragmentation of deprotonated native d-ribose and d-fructose and the isotopically labelled 1-¹³C-d-ribose, 5-¹³C-d-ribose and C-1-d-d-ribose. The fragmentation is studied in a matrix assisted laser desorption/ionization time of flight mass spectrometer (MALDI ToF MS), both in in-source decay (ISD) and post-source decay (PSD) mode and compared with fragmentation through dissociative electron attachment (DEA). Fragmentation of deprotonated monosaccharides formed in the MALDI process, as well as their transient molecular anions formed upon electron attachment are characterized by loss of different numbers of H₂O and CH₂O units. Two different fragmentation pathways leading to cross-ring cleavage are identified. Metastable decay of deprotonated d-ribose proceeds either via an X-type cleavage yielding fragment anions at m/z = 119, 100 and 89, or via an A-type cleavage resulting in m/z = 89, 77 and 71. A fast and early metastable cross-ring cleavage of deprotonated d-ribose observed in in-source decay is dominated by X-type cleavage leading mainly to m/z = 100 and 71. For dissociative electron attachment to d-ribose a sequential dissociation was identified that includes metastable decay of the dehydrogenated molecular anion leading to m/z = 89. All other fragmentation reactions in DEA to d-ribose are likely to proceed directly and on a faster timescale (below 400 ns).     

Syntheses and structural comparisons of two copper(II) complexes with the same formula having d-(+)- and d,l-1,2,2-trimethylcyclopentane-1,3-diamine ligands

Two five-coordinate copper(II) complexes, formulated as [Cu(L_a)₂Cl]BF₄ (1) and [Cu(L_b)₂Cl]BF₄ (2) having d-(+)-1,2,2-trimethylcyclopentane-1,3-diamine (L_a) and d,l-1,2,2-trimethylcyclopentane-1,3-diamine (L_b) ligands, have been synthesized and characterized. X-ray diffraction studies of 1 and 2 demonstrate that they crystallize in the different space groups (P2₁2₁2₁ for 1 and Pnma for 2), although they have identical unit cell volumes, due to the use of enantiomeric and racemic diamine ligands. One dimensional (1D) hydrogen-bond-sustained dimeric zigzag chains are formed by means of eight-membered N₂H₂CuBF₂ as well as 10-membered N₂H₄ClBF₂ hydrogen-bonded cycles. Thermal analyses for 1 and 2 are also described herein.     

Benzamidinium d-glucuronate: Spectroscopic and structural elucidation

Benzamidinium d-glucuronate (1) crystallizes in the orthorhombic space group P2₁2₁2₁ and exhibits a 3 D network with molecules linked by moderate intermolecular hydrogen bonds (HNH…O_(solvent) 2.993 Å, HNH…OCO 2.894 Å, HNH…O_(cycle) 2.844 Å, OH…NH₂ 2.931 Å, OH…O_(solvent) 2.894, 2.924 and 2.715 Å (stronger)) with participation of cations, anions and solvent molecules. The IR-band assignment of carbohydrate moieties is elucidated by a comparison between the types and bond lengths of intermolecular interactions with participation of OH groups in d-glucuronate and linear polarized IR-(IR-LD) spectroscopic data. Experimental results are supported by theoretical ab initio calculations of benzamidinium cation and d-glucuronate anion.     

Practical synthesis of 1-deoxy-d-xylulose and 1-deoxy-d-xylulose 5-phosphate allowing deuterium labelling

An optimised gram scale synthesis allows the production of 1-deoxy-d-xylulose and 1-deoxy-d-xylulose 5-phosphate with possible deuterium labelling at C-5. Such substrates are required for investigations on the mevalonate-independent 2-C-methyl-d-erythritol 4-phosphate pathway for isoprenoid biosynthesis in bacteria and chloroplasts of phototrophic eukaryotes and for the biosynthesis of vitamins B₁ (thiamine diphosphate) and B₆ (pyridoxol phosphate) in bacteria.     

New entry to pyrrolidine homoazasugars: conversion of d-arabinose into 2,5-anhydro-2,5-imino-d-glucitol via aminohomologation

The title homoazasugar, also referred as (2R,5S)-bis(hydroxymethyl)-(3R,4R)-dihydroxypyrrolidine, has been synthesized by addition of 2-lithiothiazole to the 2,3,5-tri-O-benzyl-d-arabinofuranose-derived nitrone---hydroxylamine mixture followed by reductive N-dehydroxylation and conversion of the thiazole ring into the hydroxymethyl group.     

Cyclic oligomers (macroaldonolactones) from a protected d-galactonic acid monomer

Dicyclohexylcarbodiimide-promoted self-condensation of 2,3:4,5-di-O-isopropylidene-d-galactonic acid (3) led to the macrocyclic oligomeric cyclo[(2,3:4,5-di-O-isopropylidene-(1→6)-d-galactonate)₂] (4) and cyclo[(2,3:4,5-di-O-isopropylidene-(1→6)-d-galactonate)₃] (5), having, respectively, 14- and 21-membered rings. The macrocycles 4 and 5 were also synthesized by cyclization of the respective linear dimer 11 and trimer 14 ω-hydroxy acids precursors prepared by stepwise additions of 3. Compounds 4 and 5 are biomaterials that may be described as macrolactone-cyclodextrins.     

EPR and optical absorption studies of Cr ions in d-gluconic acid monohydrate

EPR studies are carried out on Cr³⁺ ions doped in d-gluconic acid monohydrate (C₆H₁₂O₇·H₂O) single crystals at 77 K. From the observed EPR spectra, the spin Hamiltonian parameters g, |D| and |E| are measured to be 1.9919, 349 (×10⁻⁴) cm⁻¹ and 113 (×10⁻⁴) cm⁻¹, respectively. The optical absorption of the crystal is also studied at room temperature. From the observed band positions, the cubic crystal field splitting parameter Dq (2052 cm⁻¹) and the Racah interelectronic repulsion parameter B (653 cm⁻¹) are evaluated. From the correlation of EPR and optical data the nature of bonding of Cr³⁺ ion with its ligands is discussed.     

Stereo-controlled approach to pyrrolidine iminosugar C-glycosides and 1,4-dideoxy-1,4-imino-l-allitol using a d-mannose-derived cyclic nitrone

Intramolecular N-alkylation of 2,3-O-isopropylidene-5-O-methanesulfonyl-6-O-t-butyldimethylsilyl-d-mannofuranose-oxime 7 afforded a five-membered cyclic nitrone 9, which on N–O bond reductive cleavage followed by deprotection of –OTBS and acetonide functionalities gave 1,4-dideoxy-1,4-imino-l-allitol (DIA) 3. Addition of allylmagnesium chloride to nitrone 9 afforded α-allylated product 10a in high diastereoselectivity providing an easy entry to N-hydroxy-C1-α-allyl-substituted pyrrolidine iminosugar 4a after removal of protecting group, while N–O bond reductive cleavage in 10a afforded C1-α-allyl-pyrrolidine iminosugar 4b.     

Improved synthesis of 6-amino-6-deoxy-d-galactono-1,6-lactam and d-mannono-1,6-lactam from corresponding unprotected d-hexono-1,4-lactones

Regioselective bromination of unprotected d-galactono-1,4-lactone and d-mannono-1,4-lactone with PPh₃/CBr₄ led to 6-bromo-6-deoxy derivatives. These intermediates were treated with LiN₃ and hydrogenated to give 6-amino-6-deoxy-d-galactono-1,6-lactam (8) and 6-amino-6-deoxy-d-mannono-1,6-lactam (13) in 74 and 67% overall yield, respectively.     

New building blocks for peptide and depsipeptide modification N-glycosylated l-malic and l-citramalic acid derivatives

Neoglycoconjugates have been synthesized from l-malic acid/L-citramalic acid and β-d-Ac₄Glc-NH₂/β-d-Bzl₄Glc-NH₂ using hexafluoroacetone as protecting and activating agent.     

An efficient synthesis of d-ribo-C18-phytosphingosine and l-arabino-C18-phytosphingosine from d-fructose

d-ribo-C₁₈-phytosphingosine and l-arabino-C₁₈-phytosphingosine were synthesised starting from commercially inexpensive d-fructose. Metal-mediated fragmentation and stereoselective reduction were used as key steps to provide the hydrophilic portion of d-ribo and l-arabino phytosphingosines. Grubbs’ cross-metathesis and hydrogenation allowed the incorporation of hydrophobic tail.     

Stereoselective total synthesis of ophiocerin D from d-xylose

A stereoselective total synthesis of ophiocerin D is reported by a combination of a ‘chiron’ approach and an asymmetric synthesis, from d-xylose. Of the four stereogenic centers, the vic diols C3/C4 and C5/C6 were obtained by Sharpless asymmetric dihydroxylation and from d-xylose, respectively.     

Anion recognition by d-ribose-based receptors

Anion recognition properties of d-ribose-based receptors α- and β-1 were measured by ¹H NMR in CDCl₃ and MeCN-d₃. Receptor β-1 showed effective binding with anions by cooperative hydrogen bonds of cis-diol. The anomeric isomer α-1 is a less effective anion receptor which has similar cis-diol as a recognition site, indicating that the stereo configuration of the anomeric position is of significant influence on the anion recognition ability.     

Tetrahydrofuran-mediated radical processes: stereoselective synthesis of d,l-hexestrol

The highly stereoselective synthesis of d,l-hexestrol (1), an inhibitor of microtubule assembly, is developed by using, as a key step, an intermolecular coupling of Co₂(CO)₆-complexed propargyl radicals. The latter are generated by novel complementary processes involving an interaction of tetrahydrofuran with Co₂(CO)₆-complexed propargyl alcohols and cations. An isomerically pure d,l-μ-η²-[3,4-di(4-methoxyphenyl)-1,5-hexadiyne]-bis-dicobalthexacarbonyl (d,l-6) is isolated in 69-91% yield with intermolecular coupling reactions exhibiting an excellent chemo- (0.5-7%) and d,l-diastereoselectivity (90-94%). The structure of d,l-6 is determined by X-ray diffraction. The subsequent steps include BBr₃-induced demethylation of 4-methoxyaryl groups, demetalation with cerium(IV) ammonium nitrate, and hydrogenation of acetylenic termini affording d,l-hexestrol (1).     

Asymmetric syntheses of the methyl glycosides of 2-deoxy-2-aminohexoses: d-allosamine, d-mannosamine, d-idosamine and d-talosamine

A range of the methyl glycosides of 2-deoxy-2-aminohexoses, comprising d-allosamine, d-mannosamine, d-idosamine and d-talosamine, were prepared from the corresponding d-aldopentoses via a seven step synthetic sequence. The doubly diastereoselective conjugate addition of the requisite antipode of lithium N-benzyl-N-(α-methylbenzyl)amide and in situ enolate oxidation with the requisite antipode of camphorsulfonyloxaziridine (CSO) was used as the key, stereodefining step. Sequential reduction of the resultant α-hydroxy-β-amino esters and oxidative cleavage of the C(1)–C(2) diol unit furnished the corresponding α-amino aldehydes. Subsequent N- and O-deprotection gave the target compounds (as mixtures of anomers) in good yield and high diastereoisomeric purity.     

Efficient synthesis of new N-alkyl-d-ribono-1,5-lactams from d-ribono-1,4-lactone

d-Ribono-1,4-lactone was treated with ethylamine in DMF to afford N-ethyl-d-ribonamide 9a in quantitative yield. Bromination of amide 9a by the system SOBr₂ in DMF or PPh₃/CBr₄ in pyridine led, after acetylation, to epoxide 7. However, treatment of amide 9a with acetyl bromide in dioxane followed by acetylation gave 2,3,4-tri-O-acetyl-5-bromo-5-deoxyl-N-ethyl-d-ribonamide 10a. Methanolysis of 10a, with sodium methoxide, afforded the N-ethyl-d-ribonolactam 11a in 51% overall yields. Using this method, N-butyl, N-hexyl, N-dodecyl, and N-benzyl-d-ribonolactams 11b-e were obtained in good yields (48-53%).     

Building carbohydrates on the dioxanone scaffold: stereoselective synthesis of d-glycero-d-manno-2-octulose

The title compound has been synthesized via two proline-catalyzed aldol addition reactions of 2,2-dialkyl-1,3-dioxan-5-ones: the first addition to 1,3-dithiane-2-carboxaldehyde, followed by reduction to the corresponding diol, protection of the OH groups and dithiane hydrolysis afforded a protected d-ribose that was used in the second aldol addition reaction.     

Electrocatalytic response of dopamine at a dl-homocysteine self-assembled gold electrode

The gold electrode self-assembled with the homocysteine monolayer (Hcy/Au) is demonstrated to catalyze the electrochemical response of dopamine (DA) by cyclic voltammetry. A pair of well-defined redox waves was obtained and the calculated standard rate constant (k_s) is 2.1×10⁻² cm/s at the self-assembled electrode. The reduction peak of DA can be used to determine the concentration of DA in presence of ascorbic acid (AA) owing to the Hcy/Au also catalyzing the electrochemical oxidation of AA.     

Synthesis of enantiopure 2-C-methyl-d-erythritol-4-phosphate

The synthesis of enantiopure 2-C-methyl-d-erythritol-4-phosphate is disclosed. A 1,3-diol possessing a quaternary stereogenic centre, prepared stereoselectively from an acyclic tri-substituted alkene, has been utilized as a key intermediate.     

Synthesis of ent-gabosine E from d-mannose by intramolecular nitrone–olefin cycloaddition

Intramolecular nitrone–olefin cycloaddition in a mannose template followed by N–O cleavage, quaternization of the resulting amine, and finally oxidative elimination of the amino group affords, after deprotection, ent-gabosine E in enantiomerically pure form.