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.     

Synthesis and activity of two trifluorinated analogues of 1-deoxy-d-xylulose 5-phosphate

An improved synthesis of 1,1,1-trifluoro-1-deoxy-d-xylulose 5-phosphate and an access to the reduced diastereomer mixture analogues 1,1,1-trifluoro-1-deoxy-d-xylitol 5-phosphate and 1,1,1-trifluoro-1-deoxy-d-lyxitol 5-phosphate are described. Inhibitor activity of all compounds on the MEP pathway for isoprenoid biosynthesis was evaluated.     

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 4,5-disubstituted-3-deoxy-d-manno-octulosonic acid (Kdo) derivatives

In this study, a new synthetic approach to 4,5-branched Kdo trisaccharides based on the common acceptor Kdo(α2-4)Kdo was developed. The synthesis of three types of 4,5-branched trisaccharides, Hep(α1-5)[Kdo(α2-4)]Kdo, Man(α1-5)[Kdo(α2-4)]Kdo, and GalNAc(α1-5)[Kdo(α2-4)]Kdo, was achieved in good yield and high α-selectivity.     

(3R,4S)-3,4,5-Trihydroxy-4-methylpentylphosphonic acid, an isosteric phosphonate analogue of 2-C-methyl-d-erythritol 4-phosphate, a key intermediate in the new pathway for isoprenoid biosynthesis

2-C-Methyl-d-erythritol 4-phosphate (MEP) is the first intermediate in the mevalonate-independent pathway for isoprenoid biosynthesis presenting the branched C₅ isoprene skeleton. Enantiopure (3R,4S)-3,4,5-trihydroxy-4-methylpentylphosphonic acid (MEP_N), an isosteric phosphonate analogue of MEP was synthesized from 1,2-O-isopropylidene-α-d-xylofuranose.     

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.     

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.     

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.     

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 new and short synthesis of naturally occurring 1-deoxy-l-gulonojirimycin from tri-O-benzyl-d-glucal

A new and short synthesis of naturally occurring 1-deoxy-l-gulonojirimycin from tri-O-benzyl-d-glucal, via a regioselective intramolecular cyclization of an amino triol intermediate, is described. Its absolute configuration was deduced from the single crystal X-ray analysis of compound 11.     

An efficient approach to d-threo-3-hydroxyaspartic acid for the synthesis of novel l-threo-oxazolines as selective blockers of glutamate reversed uptake

An efficient, stereoselective synthetic strategy to d-threo-3-hydroxyaspartic acid was developed. Starting from l-(2S,3S)-N-benzoyl-3-hydroxyaspartic acid dimethyl ester by a Deoxo-fluor-catalyzed cyclization reaction, an inversion of configuration at the β-center (erythro isomer), was observed. A base-induced epimerization reaction led to the d-trans-isomer, which was hydrolyzed to give d-threo-3-hydroxyaspartic acid with excellent stereoselectivity and overall yield. Starting from d-threo-3-hydroxyaspartic acid, l-threo-oxazolines can be stereoselectively synthesized.     

Stereoselective synthesis of muco-quercitol, (+)-gala-quercitol and 5-amino-5-deoxy-d-vibo-quercitol from d-mannitol

Synthesis of muco-quercitol, (+)-gala-quercitol, and 5-amino-5-deoxy-d-vibo-quercitol is described from d-mannitol using ring closing metathesis and diastereoselective dihydroxylations as key steps.     

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.     

Total synthesis of cryptopyranmoscatone B1 from 3,4,6-tri-O-acetyl-d-glucal

The first stereoselective total synthesis of the natural cryptopyranmoscatone B1 has been accomplished from 3,4,6-tri-O-acetyl-d-glucal. In addition to the double cross-metathesis reaction, a tandem nucleophilic addition-diastereoselective reduction of an in situ generated oxocarbenium cation have been used as key steps to assemble the glycoside moiety of the target molecule.     

Novel formal synthesis of stereospecifically C-6 deuterated d-glucose employing configurationally stable alkoxymethyllithiums

The synthesis and testing of configurational stability of chirally monodeuterated PMB- and THP-substituted oxymethyllithiums are described. Macroscopically they are configurationally stable up to −35 °C, the limit of their chemical stability, and microscopically even up to 0 °C. Furthermore, THP-protected oxy-[D₁]methyllithium has been applied in the formal synthesis of (6R)-[6-D₁]-d-glucose (four steps, 40% yield), an example of its use as a homochiral hydroxymethyl synthon.     

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.     

A short and efficient synthesis of 1,5-anhydro-d-glucitol 6-phosphate

The important d-glucose and d-glucose 6-phosphate analogues 1,5-anhydro-d-glucitol and 1,5-anhydro-d-glucitol 6-phosphate were prepared from methyl-d-glucoside in high yield and purity. Protecting of the hydroxyl groups as their allyl ether followed by reductive cleavage of the glycosidic linkage with triethylsilane formed the protected anhydroglucitol. No ring rearrangement or ring contraction was observed during the reduction step. Using the PdCl₂-CuCl₂-activated charcoal system, the allyl ether bond was cleaved with a low loading of the catalyst (0.0025 equiv per allyl group). 1,5-Anhydro-d-glucitol 6-phosphate was prepared by the phosphylation of 1,5-anhydro-d-glucitol.     

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.     

Synthesis and kinetic evaluation of 4-deoxy-4-phosphonomethyl-d-erythronate, the first hydrolytically stable and potent competitive inhibitor of ribose-5-phosphate isomerase

4-deoxy-4-Phosphonomethyl-d-erythronate, an isosteric and hydrolytically stable analogue of the known ribose-5-phosphate isomerase inhibitor 4-deoxy-4-phospho-d-erythronate, was obtained by a 14-step synthesis from d-arabinose through an highly improved synthesis of the precursor 5-deoxy-5-phosphonomethyl-d-arabinose. The title compound appears as the first stable and potent competitive inhibitor of the enzyme catalyzed isomerization of ribose-5-phosphate to d-ribulose-5-phosphate (K_i=74 μM, K_m/K_i=100), exhibiting only a 3-fold weaker inhibitory activity than its phosphate analogue.     

Synthesis of 1-C-alkyl-α-d-glucopyranosides by Lewis acid- or Brønsted acid-catalyzed O-glycosidation

We prepared several kinds of 1-C-alkyl-2,3,4,6-tetra-O-benzyl-α-d-glucopyranose derivatives containing methyl, ethyl, n-butyl, and benzyl groups as the alkyl groups at their anomeric positions. The Lewis acid- or Brønsted acid-catalyzed O-glycosidations using them as the glycosyl donors to synthesize 1-C-alkyl-d-glucopyranosides were investigated. Using 10 mol % of triphenylmethyl perchlorate efficiently catalyzed the glycosidation of 2,3,4,6-tetra-O-benzyl-1-C-methyl-α-d-glucopyranosyl dimethylphosphinothioate. The glycosidation using the 1-C-alkyl-2,3,4,6-tetra-O-benzyl-α-d-glucopyranosyl acetates smoothly proceeded in the presence of only 5 mol % of scandium(III) trifluoromethanesulfonate. The dehydration-condensation type glycosidation using the 1-C-alkyl-2,3,4,6-tetra-O-benzyl-α-d-glucopyranoses was significantly promoted using 5 mol % of bis(trifluoromethane)sulfonimide. These glycosidations successfully afforded various 1-C-alkyl-α-d-glucopyranosides in good yields with high α-stereoselectivities.