Christian Marcus Pedersen

Direct conversion of chitin biomass to 5-hydroxymethylfurfural in concentrated ZnCl2 aqueous solution

The direct conversion of chitin biomass to 5-hydroxymethylfurfural (5-HMF) in ZnCl2 aqueous solution was studied systemically. D-Glucosamine (GlcNH2) was chosen as the model compound to investigate the reaction, and 5-HMF could be obtained in 21.9% yield with 99% conversion of GlcNH2. Optimization of the reaction parameters including the screening of 8 co-catalysts was carried out. Among them, AlCl3 and B(OH)3 improved 5-HMF yield, whereas CdCl2, CuCl2 and NH4Cl had no effect. CrCl3, SnCl4 and SnCl2 showed negative effects, i.e. lower yields. Consequently, the optimal reaction conditions were found to be 67 wt.% ZnCl2 aqueous solution, at 120 °C without co-catalyst. The reactions were further studied by in situ NMR, and no intermediate or other byproducts, except humins, were observed. Finally, the substrate scope was expanded from GlcNH2 to N-acetyl-D-glucosamine and various chitosan polymers with different molecular weights, 5-HMF yield from polymers were generally lower than that from GlcNH2.

Radical substitution with azide: TMSN3–PhI(OAc)2 as a substitute of IN3

TMSN3 and PhI(OAc)2 were found to promote high-yield azide substitution of ethers, aldehydes and benzal acetals. The reaction is fast and occurs at zero to ambient temperature in acetonitrile. However, it is essential for the reaction that TMSN3 is added subsequent to the mixture of PhI(OAc)2 and the substrate. A primary deuterium kinetic isotope effect was found for the azidonation of benzyl ethers both with TMSN3-PhI(OAc)2 and with IN3. Also a Hammett free energy relationship study of this reaction showed good correlation with sigma+ constants giving with rho-values of -0.47 for TMSN3-PhI(OAc)2 and -0.39 for IN3. On this basis a radical mechanism of the reaction was proposed.

Conformationally armed glycosyl donors: reactivity quantification, new donors and one pot reactions

The relative reactivity of conformationally armed thioglycosides is quantified.

β-Selective Mannosylation with a 4,6-Silylene-Tethered Thiomannosyl Donor

Mannosylations using the new conformationally restricted donor phenyl 2,3-di-O-benzyl-4,6-O-(di-tert-butylsilylene)-1-thio-α-D-mannopyranoside (6) have been found to be β-selective with a variety of activation conditions. The simplest activation conditions were NIS/TfOH, in which case it is proposed that the β-mannoside is formed from β-selective glycosylation of the oxocarbenium ion 25 in a B(2,5) conformation.

3-Deoxy-glucosone is an Intermediate in the Formation of Furfurals from D-Glucose.

There is a consensus that the current heavy dependence on fossil fuels is untenable because it both leads to an increase in atmospheric CO2 and climate change, and because fossil fuels are a limited resource. Therefore much attention has been given to research in biofuels, combustable organic compounds obtained from the biosphere, that is, plants. Because most of the organic material in the biosphere consists of carbohydrates, especially cellulose, the majority of this research is directed at solving the problems associated with the conversion of the carbohydrate biomass into fuels. Methods based on established fermentation technologies that convert carbohydrates into bioethanol are a more immediate solution. However, it is by no means certain that ethanol is a good or even efficient solution to the problem. Ethanol is corrosive and fermentation has a poor carbon economy (glucose = 2 EtOH + 2 CO2). [2] Therefore, much attention has been paid to the direct chemical conversion of carbohydrates, and particularly dehydrative reactions to furfurals are considered promising. The main furfural of interest is the product of the acidic dehydration of glucose: hydroxymethylfurfural (HMF). This compound has generated particular recent interest as an intermediate for new biofuels such as dimethylfuran and as a platform for biobased chemicals. Of course, realizing efficient ways to obtain HMF from biomass is the key to success, and this requires a deep understanding of the process. The acid-catalyzed dehydration of glucose to HMF is a multistep process that has been known for many years. From older literature it is clear that there are two possible mechanisms of the conversion, between which it was not possible to distinguish: one mechanism is the 3-deoxy-2-keto pathway shown in Scheme 1, where elimination of the 3-OH of glucose (1) leads to 3-deoxy-d-erythro-hex-2-ulose 3 (3-deoxyglucosone) that undergoes ring-closure and eliminations to HMF (6). The alternative mechanism is the fructose pathway shown in Scheme 2, where 1 isomerizes to fructose (8) that undergoes cyclization, reisomerization, and elimination to form 6. The latter mechanism is supported by observations that 6 is formed much faster and in higher yield from 8 than from 1, and that 8 has been observed in dehydrations of 1, so in most recent literature reports the fructose mechanism appears to prevail. Yet, the 3-deoxy mechanism is in fact more logical because it does not include any “back and forth” isomerization between C-1 and C-2. In this paper we ask the question: How good a source of HMF is 3? Older work shows that 3 does dehydrate to HMF, but otherwise little has been done in the area. Compound 3 has previously been prepared by El Khadem et al. by reaction of glucose with benzoyl hydrazine to form the oxazone S1 (Scheme S1, Supporting Information) followed by rehydrazoniation with benzaldehyde. We followed this procedure with minor changes, obtaining S1 in 75 % yield, while the second step gave us 80 % yield of 3. The product gave very poor NMR spectra consisting of at least eight compounds in aqueous solution, and previously 3 has only been characterized by conversion to the dinitrophenyl hydrazone. We performed a NaBH4 reduction of the material and obtained a mixture of d-riboand d-arabino-3-deoxy-hexitols (S2 and S3) in 74 % yield, which is consistent with the compound being essentially only 3. [a] Dr. H. Jadhav, Dr. C. M. Pedersen, Prof. T. Sølling, Prof. M. Bols Department of Chemistry, University of Copenhagen Universitetsparken 5, 2100 Kbh Ø (Denmark) Fax: (+ 45) 35 32 02 12 E-mail : bols@chem.ku.dk Supporting Information for this article is available on the WWW under http://dx.doi.org/10.1002/cssc.201100249. Scheme 1. 3-Deoxy-2-ketohexose mechanism for formation of 6.

Conformationally Armed 3,6-Tethered Glycosyl Donors: Synthesis, Conformation, Reactivity, and Selectivity

The reactivity and selectivity of 3,6-tethered glycosyl donors have been studied using acceptors with different steric and electronic characteristics. Eight (four anomeric pairs) 3,6-bridged-glycosyl donors were synthesized in high yields from their common parent sugars. The glycosylation properties were tested using at least three different acceptors and several promoter systems. Thiophenyl 2,4-di-O-benzyl-3,6-O-(di-tert-butylsilylene)-α-D-glucopyranoside gave α/β mixtures with standard NIS/TfOH mediated activation, whereas the corresponding fluoride was found to be highly β-selective, when using SnCl2/AgB(C6F5)4 as the promoter system. Mannosyl donors were highly α-selective despite the altered conformation. Galactosylations using NIS/TfOH were generally α-selective, but more β-selective using the galactosyl fluoride and depending on the acceptor used. Thiophenyl 2-azido-2-deoxy-4-O-benzyl-3,6-O-(di-tert-butylsilylene)-α-D-glucopyranoside was found to be α-selective. The reactivity of the donors was investigated using competition experiments, and some but not all were found to be highly reactive. Generally it was found that the α-thioglycosides were significantly more reactive than the β; this difference in reactivity was not found for 3,6-anhydro-, armed-(benzylated), or the classic super armed (silylated) donors. A mechanism supporting the unusual observations has been suggested.

Bradykinin does not mediate remote ischaemic preconditioning or ischaemia-reperfusion injury in vivo in man

Objective To examine whether endogenous bradykinin mediates the endothelium-dependent vasomotor dysfunction induced by ischaemia-reperfusion injury, or the protection afforded by remote ischaemic preconditioning in vivo in man. Design Randomised double-blind, cross-over study. Settings Royal Infirmary of Edinburgh, Wellcome Trust Clinical Research Facility. Patients Twenty healthy male volunteers. Interventions Subjects were randomised to intravenous infusion of the bradykinin B2 receptor antagonist, HOE-140 (100 μg/kg), or saline placebo in a double-blind, crossover trial. Ischaemia-reperfusion injury was induced in the non-dominant arm by inflating a cuff to 200 mm Hg for 20 min in all subjects. Ischaemia-reperfusion injury was preceded by three cycles of remote ischaemic preconditioning in the dominant arm in 10 subjects. Main outcome measures Bilateral forearm blood flow was assessed using venous occlusion plethysmography during intra-arterial infusion of acetylcholine (5–20 μg/min). Results Acetylcholine caused vasodilatation in all studies (p<0.05) that was attenuated by ischaemia-reperfusion injury, both in the presence (p=0.0002) and absence (p=0.04) of HOE-140. Remote ischaemic preconditioning abolished the impairment of endothelium-dependent vasomotor function induced by ischaemia-reperfusion injury. HOE-140 had no effect on the protection afforded by remote ischaemic preconditioning. Conclusions These findings do not support a major role for endogenous bradykinin, acting via the B2 kinin receptor, in the mechanism of ischaemia-reperfusion injury or the protective effects of remote ischaemic preconditioning in man. Clinical Trial Registration Information NCT00965120 and NCT00965393.

Quantifying the Electronic Effects of Carbohydrate Hydroxy Groups by Using Aminosugar Models

Methyl amino-deoxy-glycosides with α- and β-gluco, α-galacto, or α-manno stereochemistry with the amino functionality in each of the four possible non-anomeric positions have been synthesized and their pK(a) values determined by titration. These model compounds were chosen because they are the amino derivatives of the most common glycosyl acceptors. From this study it was possible to evaluate the electron density at each of the given positions in the carbohydrate and compare them. Some general trends were observed: The basicity of the amino groups decreases in the order 6-NH(2)>3-NH(2)>2-NH(2)>4-NH(2) (referring to the position). The basicity of a of an amino-deoxy-sugar generally increases when one or more substituents on the sugar ring are axial. The basicity decreases when the amine is antiperiplanar to an oxygen atom. These findings are in agreement with the observations obtained from glycosylation chemistry and the regioselective protection of sugars.

Synthesis of the Core Structure of the Lipoteichoic Acid of Streptococcus pneumoniae

Streptococcus pneumoniae LTA is a highly complex glycophospholipid that consists of nine carbohydrate residues: three glucose, two galactosamine and two 2-acetamino-4-amino-2,4,6-trideoxygalactose (AATDgal) residues that are each differently linked, one ribitol and one diacylated glycerol (DAG) residue. Suitable building blocks for the glucose and the AATDgal residues were designed and their synthesis is described in this paper. These building blocks permitted the successful synthesis of the core structure Glcβ(1-3)AATDgalβ(1-3)Glcα(1-O)DAG in a suitably protected form for further chain extension (1 b, 1 c) and as unprotected glycolipid (1 a) that was employed in biological studies. These studies revealed that 1 a as well as 1 lead to interleukin-8 release, however not via TLR2 or TLR4 as receptor.

Rhamnosylation: diastereoselectivity of conformationally armed donors.

The α/β-selectivity of super-armed rhamnosyl donors have been investigated in glycosylation reactions. The solvent was found to have a minor influence, whereas temperature was crucial for the diastereoselectivity. At very low temperature, a modest β-selectivity could be obtained, and increasing temperature gave excellent α-selectivity. The donors were highly reactive, and activation was observed at temperatures as low as -107 °C. Different promoter systems and leaving groups were investigated, and only activation with a heterogeneous catalyst increased the amount of the β-anomer significantly. By introducing an electron-withdrawing nonparticipating group, benzyl sulfonyl, on 2-O, an increase in β-product was observed.