Practical synthesis of d-[1-C]mannose, l-[1-C] and l-[6-C]fucose

The chemical synthesis of ¹³C-labeled mannose and fucose is important for the preparation of molecular probes used in the conformational study of the oligosaccharide portions of glycoproteins. A new method for the synthesis of the title [1-¹³C]-labeled compounds via the corresponding olefin compounds, which are in turn derived from d-mannitol or l-arabinose by efficient introduction of ¹³C, by the Wittig reaction using Ph₃P¹³CH₃I and n-BuLi, is described. The introduction of ¹³CH₃I to produce the [1-¹³C]- and [6-¹³C]-labeled compounds was accomplished in 62%, 56%, and 71% yields, respectively. All mannose and fucose protons, from H-1 to H-6, were observed by the HMQC-TOCSY technique using 1:1 mixtures of [1-¹³C]- and [6-¹³C]-labeled compounds.     

Chemoenzymatic synthesis of [3,9-C]-labeled NeuAc and KDN

The chemoenzymatic synthesis of ¹³C-labeled sialic acid (NeuAc) and 3-deoxy-d-glycero-d-galacto-2-nonulosonic acid (KDN) as useful molecular probes for studying the conformation of sialyl or KDN oligosaccharides attached to proteins was performed by using [6-¹³C]-ManNAc, [6-¹³C]-Man and [3-¹³C]-pyruvic acid sodium salt. In the synthesis of the compounds, 5,6-anhydro intermediates were found to easily provide not only 6-¹³C-labeled but also 5-, and 6-modified NeuAc and KDN analogs. Furthermore, it was demonstrated that identical results are obtained by NMR for both [3,9-¹³C]-NeuAc and 1:1 mixtures of [3-¹³C]- and [9-¹³C]-NeuAc.     

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.     

Stereoselective synthesis of farnesylphosphoryl β-d-arabinofuranose

Decaprenylphosphoryl β-d-arabinofuranose (DPA) is a key arabinose donor in mycobacteria. In an effort to establish a practical synthetic scheme for DPA, the synthesis of nerylphosphoryl and farnesylphosphoryl β-d-arabinofuranoses has been developed. The products were obtained by coupling of a suitably protected β-d-arabinofuranosyl phosphate intermediate with activated forms of the C₁₀ nerol and C₁₅trans,trans-farnesol and subsequent deprotection.     

6-Azido d-galactose transfer to N-acetyl-d-glucosamine derivative using commercially available β-1,4-galactosyltransferase

A new strategy to tag glycoproteins carrying terminal GlcNAc was developed using commercially available bovine β-1,4-galactosyltransferase (GalT) and UDP-6-azidogalactose. The azide function was then allowed to react via a biotinylated Staudinger-Bertozzi probe demonstrating the usefulness of such a procedure to tag any glycoprotein possessing a N-acetylglucosamine terminal residue from any type of cell lysate.     

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.     

Synthesis of hybrids of d-glucose and d-galactose with 1-deoxynojirimycin analogues using ring-closing metathesis

Four hybrids of azasugars with d-glucose and d-galactose have been synthesized from 3-nitro-2,3-unsaturated-O-glycosides. All the hybrid molecules showed moderate activity against β-galactosidase, the one derived from d-glucose and 1,4-dideoxygulonojirimycin 18, and 26, which is a hybrid of d-glucose and 1,4-dideoxymannohomonojrimycin, showed selectivity toward α-glucosidase and β-galactosidase, respectively.     

The synthesis of novel hexa-C-labelled glucosinolates from [C6]-d-glucose

An isotopically labelled building block, 2,3,4,6-tetra-O-acetyl-1-thio-β-d-[¹³C₆]glucopyranose (4), is obtained from the commercially available [¹³C₆]-d-glucose. This hexa-¹³C-labelled thioglucose can be employed to make any glucosinolate (8) for use as an internal standard for isotopic dilution LCMS analysis. Herein three typical glucosinolates in their hexa-¹³C-labelled form: [glucose-¹³C₆]gluconasturtiin, [glucose-¹³C₆]sinigrin and [glucose-¹³C₆]glucoerucin are synthesised by coupling the isotopically labelled thioglucose (4) with the corresponding hydroximoyl chlorides followed by sulfation with pyridine sulfur trioxide and deacetylation with a catalytic amount of potassium methoxide, respectively.     

Facile synthesis of 6a-carba-β-d-fructopyranose through an RCM approach

A new synthetic approach toward 6a-carba-β-d-fructopyranose, a non-nutritive sweetener related to topiramate, is described. This scheme uses 2-C-hydroxymethyl-l-erythrose acetonide as starting material and efficiently delivers the target compound applying an RCM protocol for the construction of the carbocycle ring.     

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.     

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.     

Synthesis of C-disaccharide analogues of the α-d-arabinofuranosyl-(1→5)-α-d-arabinofuranosyl motif of mycobacterial cell walls via alkynyl intermediates

Two C-glycosides related to the recurrent α-d-arabinofuranosyl-(1→5)-α-d-arabinofuranosyl structural motif of mycobacterial arabinan have been prepared by routes involving acetylenic intermediates.     

Selective interactions of 18-crown-6 with d-glucose and d-galactose in aqueous solutions: Titration calorimetry, densimetry, viscosimetry

Titration calorimetric, densimetric and viscosimetric measurements have been combined to study the interactions of 18-crown-6 with d-glucose and d-galactose in water. The crown ether forms a thermodynamically stable 1:1 complex with d-galactose but not with d-glucose. These observations are explained in terms of the stereochemistry of the monosaccharide molecules.     

A chemo-enzymatic cascade for the one-pot synthesis of 1-deoxy-d-xylulose 5-phosphate and 1-deoxy-d-xylulose

A chemo-enzymatic cascade for the one-pot preparation of 1-deoxy-d-xylulose 5-phosphate (DXP) and 1-deoxy-d-xylulose (DX) from stable, cheap, and easily available starting material R-glycidol is reported. The epoxide ring of R-glycidol was opened with phosphate to generate l-glycerol 3-phosphate, which was subsequently converted into the target molecules by combination of multi-enzymatic reactions in the same flask with purified overall yields of 27.6% (DXP) and 33% (DX), respectively. This approach represents the first one-pot chemo-enzymatic synthesis of these two biologically important compounds.     

Regioselective acylation of 6-O-protected octyl β-d-glucopyranosides by DMAP catalysis

Regioselectivity of acylation of 6-O-protected octyl β-d-glucopyranosides was investigated. Treatment of octyl 6-O-methyl-β-d-glucopyranoside with isobutyric anhydride in the presence of DMAP in toluene at −40 °C gave 3-O-isobutyryl derivative in >99% regioselectivity. Similar treatment of octyl 6-O-TBS-β-d-glucopyranoside at −20 °C also gave 3-O-isobutyryl derivative in >99% regioselectivity.     

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.     

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.     

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.     

Practical synthesis of valuable d-rhamnoside building blocks for oligosaccharide synthesis

The efficient synthesis of d-rhamnoside and the corresponding methods for its regioselective protections and deprotections have been developed in order to provide key building blocks for complex oligosaccharide syntheses toward vaccines against bacterial infections.     

Synthesis of carba analogs of 6-O-(benzyl)-d-allal- and -d-galactal-derived allyl epoxides and evaluation of the regio- and stereoselective behavior in nucleophilic addition reactions

The new racemic diastereoisomeric epoxides 6α and 6β, the carba analogs of the corresponding d-galactal- and d-allal-derived allyl epoxides have been synthesized and their regio- and stereoselective behavior examined in addition reactions with model O-, C-, N-, and S-nucleophiles. The results have indicated that epoxide 6β has a pronounced tendency toward anti-1,2-addition, whereas epoxide 6α shows interesting levels of syn- and/or anti-1,4-addition processes. A chiral recognition process found with epoxide 6β, turned out to be consistently reduced in epoxide 6α. All the results have been rationalized on the basis of conformational, steric, and stereoelectronic effects.