Synthesis and chromatographic study of methyl-2,3-O-isopropylidene-5-dimethyl-arsinoyl-β-d-ribofuranoside and methyl-2,3-O-isopropylidene-5-deoxy-5-dimethyl-thioarsinoyl-β-d-ribofuranoside

The synthesis of two riboside-containing arsenic compounds, methyl-2,3-O-isopropylidene-5-dimethyl-arsinoyl-β-d-ribofuranoside and methyl-2,3-O-isopropylidene-5-deoxy-5-dimethyl-thioarsinoyl-β-d- ribofuranoside is presented in this paper. Intermediates and final products of the synthesis were examined by gas chromatography and thin layer chromatography. The purity of the products was assessed by NMR spectroscopy. Trimethylsilylation was used to volatilise sugar compounds and thus use of the costly HPLC–MS technique was avoided. The results affirmed the presence of tautomers in case of arsenosugars.     

An efficient synthesis of l-allono-1,4-lactone from 2,3:5,6-di-O-isopropylidene-d-mannono-1,4-lactone

We reported herein an efficient synthesis of l-allono-1,4-lactone from 2,3:5,6-di-O-isopropylidene-d-mannono-1,4-lactone in five steps. The key feature of this method involved a one-pot, ‘double inversion’ procedure at the stereocenters of C-4 and C-5 of d-mannono-1,4-lactone to afford the target molecule.     

Synthesis of orthogonally protected d-olivoside, 1,3-di-O-acetyl-4-O-benzyl-2,6-dideoxy-d-arabinopyranose, as a C-glycosyl donor

1,3-Di-O-acetyl-4-O-benzyl-2,6-dideoxy-d-arabinopyranose (11) was synthesised from thiophenyl α-d-mannopyranoside (21) in an eight-step sequence. Tosylation of 21 and subsequent reaction with 2,2-dimethoxypropane gave tosylate 22, which upon treatment with lithium aluminium hydride furnished 6-deoxy glycoside 24 and by-product thiophenyl 6-deoxy-2-O-isopropyl-α-d-arabinopyranoside. The X-ray crystal structure of the latter was determined. Benzylation of the 4-hydroxyl group of 24 and subsequent protecting group manipulation gave d-rhamnosyl bromide 29, which on treatment with zinc-copper couple gave the orthogonally protected d-rhamnal 30. Triphenylphosphine hydrogen bromide catalysed addition of acetic acid to 30 furnished the target molecule 11. The scandium(III) triflate promoted reaction of 11 and 2-naphthol gave the corresponding C-glycoside 36 in 86% yield.     

From d-xylose to a d-glycero-l-altrose derivative

A key intermediate corresponding to a rare sugar framework has been synthesized, starting from d-xylose, an inexpensive carbohydrate. This approach gave access to new elaborated sugar moieties for structure–activity relationships in the KRN research.     

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.     

Selection of synthetic receptors capable of sensing the difference in binding of d-Ala-d-Ala or d-Ala-d-Lac ligands by screening of a combinatorial CTV-based library

Screening of a combinatorial CTV-based artificial, synthetic receptor library 1 {1-13, 1-13, 1-13} for binding of a variety d-Ala-d-Ala and d-Ala-d-Lac containing ligands (6-11) was carried out in phosphate buffer (0.1 N, pH=7.0). After screening and Edman sequencing, synthetic receptors were found containing amino acid sequences, which are either characteristic for binding dye labeled d-Ala-d-Ala or d-Ala-d-Lac containing ligands. For example, receptors capable of binding d-Ala-d-Ala containing ligands 6, 7, 9 and 11 contained—almost in all cases—at least one basic amino acid residue—predominantly Lys—in their arms. This was really a striking difference with the arms of the receptors capable of binding d-Ala-d-Lac containing ligands 8 and 10, which usually contained a significant number of polar amino acids (Gln and Ser), especially in ligand 8, but hardly any basic amino acids. Use of different (fluorescent) dye labels showed that the label has a profound, albeit not decisive, influence on the binding by the receptor. A hit from the screening of the CTV-library with FITC-peptidoglycan (6) was selected for resynthesis and validation.     

Concise and stereocontrolled syntheses of phosphonate C-glycoside analogues of β-d-ManNAc and β-d-GlcNAc 1-O-phosphates

Diethyl C-(2-deoxy-2-acetamido-β-d-mannopyranosyl)methylphosphonate and dimethyl C-(2-deoxy-2-acetamido-β-d-glucopyranosyl)methylphosphonate were stereoselectively prepared from N-acetyl d-glucosamine. Routes to such compounds starting from d-GlcNAc have been problematic, but we have found short and efficient implementations of this highly desirable transformation.     

Henry condensations with 4,6-O-benzylidenylated and non-protected d-glucose and l-fucose via DBU-catalysis

Mechanistic intermediates, and thermodynamically favored side products, in the Henry condensations of partially protected and non-protected pyranoses with a free anomeric hemiacetal function with nitromethane in various solvents for the kinetically controlled syntheses of C-glycopyranosides in the presence of DBU/molecular sieve catalyst system were identified.     

An efficient synthesis of d-ribo- and l-lyxo-phytosphingosine from d-tartaric acid

The preparations of d-ribo- and l-lyxo-phytosphingosines (1, 2) are described. Chelation-controlled addition of tetradecylmagnesium bromide to pentylidene-protected d-threitol aldehyde 6 afforded the key intermediate tetrol 7, providing the desired l-lyxo stereochemistry of phytosphingosine. Inversion at C4 of intermediate 7 provided the d-ribo stereochemistry.     

Highly efficient stereoselective synthesis of d-erythro-sphingosine and d-lyxo-phytosphingosine

Starting from a single suitable functionalised epoxide, a highly efficient stereoselective synthesis of d-erythro-sphingosine and d-lyxo-phytosphingosine is described. The approach allows the formal preparation of all stereoisomers of these sphingoid structures.     

Stereoselective synthesis of 3-glycosyl-5-methoxycarbonyl-isoxazolidines from d-galactose and d-glucose

Regio- and stereoselective cycloaddition of methyl acrylate to C-glycosyl nitrones derived from d-galactose and d-glucose, giving 5-methoxycarbonyl-3-(pentoglycos-5-yl or pentitol-1-yl)isoxazolidines, is reported. Transformation of one of them into a 4-hydroxy-2-(pentoglycos-5-yl)pyrrolidine derivative, potentially useful in a route to polyhydroxy-perhydroazaazulenes, was achieved.     

A convenient synthesis of methyl N-acetyl-α-d-lividosaminide from d-glucal

Methyl N-acetyl-α-d-lividosaminide has been synthesised starting from 4,6-di-O-benzyl-d-glucal via a new nitro glucal derivative in six steps.     

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.     

Novel synthesis of 5-thio-hexopyranoside: preparation of 5-thio-d- and l-glucose and 1,6-anhydro-5-thio-l- and d-altrose

Asymmetric synthesis of both d- and l-isomers of 5-thioglucose and 1,6-anhydro-5-thioaltrose are described. The key intermediates, l- and d-threose diethylacetal derivatives, were derived by chemical transformation from d-xylose or d-arabinose and by Sharpless asymmetric dihydroxylation from γ-hydroxycrotylaldehyde diethylacetal. They transformed to γ-thiiranyl diethylacetal via trans-2,3-epoxy alcohol in seven steps. Acetic acid-promoted cyclization of γ-thiiranyl diethylacetal gave 5-thiopyranoside. Removal of the protected groups under the acidic conditions afforded 5-thio-d- and l-glucose and 1,6-anhydro-5-thio-l- and d-altrose, respectively.     

A convenient synthesis of l-ribose from d-fructose

An efficient method for the stereoselective synthesis of l-ribose was accomplished starting from commercially inexpensive d-fructose. The intermediates in the process can serve as versatile precursors for the preparation of l-nucleoside analogues.     

Enantiospecific enzymatic synthesis of N-carbamoyl-d-p-fluorophenylglycine and N-carbamoyl-d-p-trifluoromethylphenylglycine

Enantiospecific enzymatic hydrolysis of rac-5-arylhydantoins is described. Immobilized d-hydantoinase from Vigna angularis was used to produce with 100% conversion and over 98% enantiomeric excess N-carbamoyl-d-p-fluorophenylglycine and N-carbamoyl-d-p-trifluoromethylphenylglycine.     

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%).     

Asymmetric syntheses of 6-deoxyfagomin, d-deoxyrhamnojirimycin, and d-rhamnono-1,5-lactam

N-Allyl protected 3-O-benzyloxglutarimide 11 was synthesized as a useful variant of the chiral building block 10. This modification allowed a high-yielding deprotection of the allyl group from the lactam intermediate 14. Starting from this building block, the asymmetric syntheses of aza-sugars 6-deoxyfagomine (2), d-rhamnono-1,5-lactam (6), as well as d-deoxyrhamnojirimycin (5) have been achieved in high regio- and/or diastereo-controlled manner.     

First phosphorous d-xylose-derived glycodendrimers

Phosphorous glycodendrimers have been prepared in quantitative yields by grafting xylose-derived moieties on phosphorous dendrimers involving hydrazone units. These dendrimers could be hydrophobic or amphiphilic, respectively, with acetylated or unprotected sugar moieties.     

An efficient synthesis of 1,4-dideoxy-1,4-imino-d- and l-arabinitol and 1,4-dideoxy-1,4-imino-d- and l-xylitol from chiral aziridines

A highly efficient method for the synthesis of 1,4-dideoxy-1,4-imino-d- and l-arabinitol (d-AB1, 1 and l-AB1, 3) and 1,4-dideoxy-1,4-imino-d- and l-xylitol (d-DIX, 2 and l-DIX, 4) starting from commercially available chiral aziridines was developed. The general strategy employs a sequence involving two-carbon homologation, dihydroxylation, and regioselective aziridine ring opening/intramolecular five-membered iminosugar ring formation. The facile use of recrystallization to generate pure diastereomers makes the routes more amenable to large-scale synthesis.