Retro Aldol Research Articles

New reaction pathways for high selectivity synthesis of methyl lactate via SnClx(OH)2-x-catalyzed cellulose conversion in water-containing methanol solution

Catalytic conversion of cellulose into lactic acid (LA) is paramount for the emerging biomass-based chemical industry. With emphasis on the reaction mechanism, the catalytic cellulose conversion to methyl lactate (ML) was systematically investigated in water-containing methanol solution. The role that water plays and catalytic mechanism of the acidic and basic sites were analyzed and discussed. It was found that water played an important role in modulating hydrolysis of SnCl2 to release H+ protons and basic SnClx(OH)2-x species. These basic species are very efficient for the isomerization and [3+3] retro aldol condensation in terminal glucose units of cellulose chain, while H+ protons facilitate the ring-opening of the ends of cellulose chains to trioses rather than hydrolysis of the glucoside bonds to form glucose. Based on advanced characterization techniques including ESI-MS, GPC, FT-IR, XRD, XPS and CP-MAS 13C NMR as well as DFT calculations, two new reaction pathways were disclosed for the first time, which are distinct from the well-known traditional pathway that goes through the formation of glucose. Owing to the exclusion of the formation of glucose during the cellulose conversion, the selectivity towards ML can be greatly enhanced. Under optimal conditions, the total selectivity could reach to 91.5 % with a ML and LA yield of 66.3 %. These findings provide new insights into the catalytic conversion of cellulose into value-added chemicals and help explore effective catalysts.

Transient Metallo-Lipidoid Assemblies Amplify Covalent Catalysis of Aqueous and Non-Aqueous Reactions.

Dissipative supramolecular assemblies are hallmarks of living systems, contributing to their complex, dynamic structures and emerging functions. Living cells can spatiotemporally control diverse biochemical reactions in membrane compartments and condensates, regulating metabolite levels, signal transduction or remodeling of the cytoskeleton. Herein, we constructed membranous compartments using self-assembly of lipid-like amphiphiles (lipidoid) in aqueous medium. The new double-tailed lipidoid features Cu(II) coordinated with a tetravalent chelator that dictates the binding of two amphiphilic ligands in cis-orientation. Hydrophobic interactions between the lipidoids coupled with intermolecular hydrogen bonding led to a well-defined bilayer vesicle structure. Oil-soluble SNAr reaction is efficiently upregulated in the hydrophobic cavity, acting as a catalytic crucible. The modular system allows easy incorporation of exposed primary amine groups, which augments the catalysis of retro aldol and C-N bond formation reactions. Moreover, a higher-affinity chelator enables consumption of the Cu(II) template leveraging the differential thermodynamic stability, which allows a controllable lifetime of the vesicular assemblies. Concomitant temporal upregulation of the catalytic reactions could be tuned by the metal ion concentration. This work offers new possibilities for metal ion-mediated dynamic supramolecular systems, opening up a massive repertoire of functionally active dynamic "life-like" materials.

Transient Metallo‐Lipidoid Assemblies Amplify Covalent Catalysis of Aqueous and Non‐Aqueous Reactions

AbstractDissipative supramolecular assemblies are hallmarks of living systems, contributing to their complex, dynamic structures and emerging functions. Living cells can spatiotemporally control diverse biochemical reactions in membrane compartments and condensates, regulating metabolite levels, signal transduction or remodeling of the cytoskeleton. Herein, we constructed membranous compartments using self‐assembly of lipid‐like amphiphiles (lipidoid) in aqueous medium. The new double‐tailed lipidoid features Cu(II) coordinated with a tetravalent chelator that dictates the binding of two amphiphilic ligands in cis‐orientation. Hydrophobic interactions between the lipidoids coupled with intermolecular hydrogen bonding led to a well‐defined bilayer vesicle structure. Oil‐soluble SNAr reaction is efficiently upregulated in the hydrophobic cavity, acting as a catalytic crucible. The modular system allows easy incorporation of exposed primary amine groups, which augments the catalysis of retro aldol and C−N bond formation reactions. Moreover, a higher‐affinity chelator enables consumption of the Cu(II) template leveraging the differential thermodynamic stability, which allows a controllable lifetime of the vesicular assemblies. Concomitant temporal upregulation of the catalytic reactions could be tuned by the metal ion concentration. This work offers new possibilities for metal ion‐mediated dynamic supramolecular systems, opening up a massive repertoire of functionally active dynamic “life‐like” materials.

Nickel-tungsten co-doped biochar catalyst boosting ethylene glycol production from cellulose hydrogenolysis

Promoted ethylene glycol (EG) yield from cellulose hydrogenolysis is achieved via using Nickel-tungsten doped carbon catalysts prepared from glucose (x%Ni-y%WOx-GCT). Synchronously metal loading and carbon formation endow the catalyst excellent catalytic performance and high stability. Mechanistic investigations of the effects of metal loading and BrØnsted acid on EG yield are conducted. Increasing W loading promotes the content of polymerized WOx and consequently increases the amount of polytungstate species, thus lead to an improved BrØnsted acid content. Results reveal that promotion of B/L acid facilitates cellulose hydrolysis and suppresses isomerization of glucose to fructose. Besides, high W loading is beneficial for reduction of WOx to form W5+, producing oxygen vacancies to promote retro aldol condensation (RAC) of glucose to form acetaldehyde alcohol (an important intermediate for EG). By adopting the optimized 9%Ni-12%WOx-GC700 catalyst, a 100% cellulose conversion with a high EG yield of 65% is obtained due to the synergistic interactions between BrØnsted acid, W5+ and Ni0+ active sites.

Characterization of thermostable serine hydroxymethyltransferase for β-hydroxy amino acids synthesis

β-hydroxy amino acids, such as serine, threonine, and phenylserine, are important compounds for medical purposes. To date, there has been only limited exploration of thermostable serine hydroxylmethyltransferase (SHMT) for the synthesis of these amino acids, despite the great potential that thermostable enzymes may offer for commercial use due to their high stability and catalytic efficiencies. ITBSHMT_1 (ITB serine hydroxylmethyltransferase clone number 1) from thermophilic and methanol-tolerant bacteria Pseudoxanthomonas taiwanensis AL17 was successfully cloned. Biocomputational analysis revealed that ITBSHMT_1 contains Pyridoxal-3′-phosphate and tetrahydrofolatebinding residues. Structural comparisons show that ITBSHMT_1 has 5 additional residues VSRQG on loop near PLP-binding site as novel structural feature which distinguish this enzyme with other characterized SHMTs. In silico mutation revealed that the fragment might have very essential role in maintaining of PLP binding on structure of ITBSHMT_1. Recombinant protein was produced in Escherichia coli Rosetta 2(DE3) in soluble form and purified using NiNTA affinity chromatography. The purified protein demonstrated the best activity at 80 °C and pH 7.5 based on the retro aldol cleavage of phenylserine. Activity decreased significantly in the presence of 3 mM transition metal ions but increased in the presence of 30 mM β-mercaptoethanol. ITBSHMT_1 demonstrated Vmax, Km, Kcat, and Kcat/Km at 242 U/mg, 23.26 mM, 186/s, and 8/(mM.s), respectively. The aldol condensation reaction showed the enzyme’s best activity at 80 °C for serine, threonine, or phenylserine, with serine synthesis showing the highest specific activity. Biocomputational analysis revealed that high intramolecular interaction within the 3D structure of ITBSHMT_1 might be correlated with the enzyme’s high thermal stability. The above data suggest that ITBSHMT_1 is a potential and novel enzyme for the production of various β-hydroxy amino acids.

Bioconjugation with Aminoalkylhydrazine for Efficient Mass Spectrometry-Based Detection of Small Carbonyl Compounds.

Bioconjugation through oxime or hydrazone formation is a versatile strategy for covalent labeling of biomolecules in vitro and in vivo. In this work, a mass spectrometry-based method was developed for the bioconjugation of small carbonyl compounds (CCs) with an aminoalkylhydrazine to form stable hydrazone conjugates that are readily detectable with electrospray ionization mass spectrometry (ESI-MS). Out of all hydrazine reagents tested, 2-(dimethylamino)ethylhydrazine (DMAEH) was selected for further analysis due to the fastest reaction rates observed. A thorough study of the reaction kinetics between structurally varied short-chain CCs and DMAEH was performed with the second-order reaction rate constants spanning in the range of 0.23–208 M–1 s–1. In general, small aldehydes reacted faster than the corresponding ketones. Moreover, a successful reaction monitoring of a deoxyribose-5-phosphate aldolase-catalyzed reversible retro–aldol cleavage of deoxyribose was demonstrated. Thus, the developed method shows potential also for ESI-MS-based enzyme kinetics studies.

Hydrothermal gasification of xylose: Effects of reaction temperature, pressure, and K2CO3 as a catalyst on product distribution

The hydrothermal gasification of xylose, as a model substance for the main polysaccharide in hemicelluloses, was carried out at high temperatures (up to 600 °C) and high pressures (up to 42.5 MPa) in the presence of an alkali catalyst with a constant reaction time of 3600 s. The comparison of the experimental results, such as the volume of the gas phase, composition of the gas, and the liquid products together with the total organic carbon content (TOC) provides the knowledge of the chemical reaction pathways of the xylose and their dependence on the reaction conditions, temperature, pressure, and catalyst. Both the gas and liquid phases were analyzed using chromatographic techniques. The major gaseous compounds produced were hydrogen, methane, carbon dioxide, carbon monoxide and C2C4 hydrocarbons. The carbon gasification efficiencies were improved by increasing the temperature and decreasing the pressure and reached their maximum value (86%) at 20 MPa and 600 °C with the addition of K2CO3. The highest measured concentration of the retro aldol reaction product was acetic acid and the dehydration product was 5-methyl furfural.

Synthesis of 4-aryl-1,7-dihydroxyalkane-2,6-diones under aldol reaction conditions

Reactions of 3-hydroxyalkan-2-ones with (hetero)aromatic aldehydes under basic conditions lead to 4-aryl-1,7-dihydroxyalkane-2,6-diones. These products were also synthesized by dismutation of 4-aryl-1-hydroxyalk-3-ene-2-ones. The reactions proceed as tandem retro aldol reactions and the Michael addition.

Density Functional Theory (DFT) study on the pyrolysis of cellulose: The pyran ring breaking mechanism

Pyran ring breaking is a key step for cellulose pyrolysis to produce small molecular products. Cellotriose was employed as the model compound of cellulose to explore the mechanism of pyran ring breaking based on Density Functional Theory (DFT). Four kinds of reaction mechanisms were studied: (1) directly breaking mechanism, (2) Retro–Diels–Alder mechanism, (3) C6OH assisted pinacol ring cleavage mechanism and (4) Retro–Aldol mechanism. The calculated results showed that pyran ring break via Retro–Aldol mechanism (with C3O formed) was kinetically favored over Retro–Diels–Alder mechanism (with C3C4 bond formed), followed by C6OH assisted pinacol ring cleavage mechanism, 2′+2′+2′ and 2+2+2 mechanism. Activation energies for both of the two-step mechanisms, Retro–Diels–Alder and Retro–Aldol, varied on the positions of CC bond and CO group formed. The results provided a better understanding on pyran ring breaking mechanism during cellulose pyrolysis.

Pressure and temperature effect on cellulose hydrolysis in pressurized water

In this study, the effect of temperature and pressure on cellulose and glucose hydrolysis in a hydrothermal media was analyzed. To do so, cellulose hydrolysis experiments were carried out in a continuous pilot plant capable of operating up to 400°C and 27MPa. The reaction times were varied between 0.004 and 40s. The main products of cellulose hydrolysis were oligosaccharides, cellobiose, glucose and fructose. The concentration profiles of each component followed a similar behavior at a fixed temperature changing pressure. Nevertheless, glucose and fructose hydrolysis reaction to give dehydration of retro aldol condensation products were strongly affected by pressure and temperature. When increasing temperature in the studied range, the reaction of glucose isomerization to fructose and the production of 5-hydroxymethylfurfural (5-HMF) obtained through fructose dehydration were inhibited. On the other hand, 5-HMF production was favored by high proton concentrations due to water dissociation. Thus, at a constant temperature, the production of 5-HMF was increased by rising the ionic product of water (increasing pressure). The production of glycolaldehyde (retro-aldol condensation of glucose) was increased by rising temperature and pressure. The kinetic constants of the cellulose hydrolysis reactions were determined at the experimented conditions using the experimental results. The kinetic constants were plotted against temperature and pressure to determine the activation energy and the activation volume for each reaction, respectively. Pressure seems to have no effect on the cellulose hydrolysis kinetic to simple sugars. However, at supercritical water temperatures the increment in pressure disfavored the glucose isomerization and dehydration reactions.

ChemInform Abstract: Secondary Amine Catalyzed Retro‐Aldol Reactions of Enals and Enones: One‐Pot Conversion of Enals to α‐Substituted Derivatives.

AbstractOptimized conditions which include pyrrolidine as the promoter allow the retro aldol hydrolysis of cinnamaldehydes and aliphatic α,β‐unsaturated aldehydes.

Sn-Beta catalysed conversion of hemicellulosic sugars

Conversions of various pentoses and hexoses into methyl lactate has been demonstrated for the Sn-Beta catalyst. It is found that pentoses are converted to methyl lactate in slightly lower yields (∼40%) than what is obtained for hexoses (∼50%), but higher yields of glycolaldehyde dimethyl acetal are observed for the pentoses. This finding is in accordance to a reaction pathway that involves the retro aldol condensation of the sugars to form a triose and glycolaldehyde for the pentoses, and two trioses for hexoses. When reacting glycolaldehyde (formally a C2-sugar) in the presence of Sn-Beta, aldol condensation occurs, leading to the formation of methyl lactate, methyl vinylglycolate and methyl 2-hydroxy-4-methoxybutanoate. In contrast, when converting the sugars in water at low temperatures (100 °C), Sn-Beta catalyses the isomerisation of sugars (ketose–aldose epimers), rather than the formation of lactates.

Cyclization of Synthetic seco‐Proansamitocins to Ansamitocin Macrolactams by Actinosynnema pretiosum as Biocatalyst

Cyclization of Synthetic <i>seco</i>‐Proansamitocins to Ansamitocin Macrolactams by <i>Actinosynnema pretiosum</i> as Biocatalyst

Synthesis of 2,2’-(ethane-l,l-diyl)bis(3,5,6,7,8-pentahydroxy-l,4-naphthoquinone), a metabolite of the sea urchins Spatangus purpureus, Strongylocentrotus intermedius, and S. droebachiensis

A key step in the synthesis of 2,2’-(alkane-l,l-diyl)bis(3,5,6,7,8-pentahydroxy-l,4-naphthoquinones) is an acid-catalyzed condensation of 2-hydroxynaphthazarins, the products of the retro aldol reaction of 2-hydroxy-3-(l-hydroxyalkyl)naphthazarins, with the corresponding aldehydes. This method is applicable, in particular, for the preparation of compound with the ethane-1,1-diyl bridge — a metabolite produced by the sea urchins Spatangus purpureus, Strongylocentrotus intermedius, and S. droebachiensis.

Vapor-phase catalytic reactions of alcohols over bixbyite indium oxide

Vapor-phase catalytic reactions of several alcohols were investigated over In 2O 3. In 2O 3 showed stable catalytic activity in the dehydration of terminal diols, such as 1,4-butanediols and 1,5-pentanediol, to produce unsaturated alcohols, such as 3-buten-1-ol and 4-penten-1-ol, respectively, with selectivities higher than 70 mol%. Although the dehydration of 1,3-diols, such as 1,3-propanediol and 1,3-butanediol, also proceeded over In 2O 3, the catalytic activity decreased with time on stream because of dehydrogenation followed by retro aldol reaction of the resulting dehydrogenated products. In contrast, in the reaction of monoalcohols, such as 1-butanol and 2-octanol, dehydrogenation dominantly proceeded to produce butanal and 2-octanone, respectively. Although In 2O 3 has cubic bixbyite crystal structure that is the same as those of heavy rare earth oxides, the catalytic activity of In 2O 3 was similar to that of cubic fluorite CeO 2 with redox property, rather than those of heavy rare earth oxides with acid–base property. Redox sites of In 2O 3 are concluded to be active centers for the dehydration of diols to produce unsaturated alcohols.

Multiple catalytic aldolase antibodies suitable for chemical programming

Chemical programming of nine murine antibodies with catalytic aldolase activity was examined using compounds, equipped with diketone or pro-vinyl ketone linkers that inhibit integrin adhesion receptor functions. The results showed that most Abs were programmed using the diketone compounds in a manner similar to previously reported catalytic antibody 38C2. On the other hand, only those antibodies, which catalyzed the retro aldol reaction of the pro-vinyl ketone linkers efficiently, were programmed. Conjugated to integrin targeting compounds, at least three new antibodies, including 84G3, 85H6, and 90G8, exhibited high specific binding to human tumor cells expressing integrin α vβ 3.

Helical primary structures of 1,2-spiroannelated five-membered rings: attempted synthesis of (±)-tetraspiro[4.0.0.0.4.3.3.3]heneicosane

A β-hydroxy ketone with a helical carbon skeleton of five 1,2-spiroannelated cyclopentane rings is the main product of a Lewis acid catalyzed rearrangement of suitable sized α-hydroxy epoxides followed by an in situ equilibration via retro aldol reactions. Various attempts of a conversion to the title hydrocarbon failed.

A New and Efficient One‐Pot Solid‐Supported Synthesis of 1,2,4,6‐Tetraaryl‐1,4‐dihydropyridines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A new and efficient one-pot solid-supported synthesis of 1,2,4,6-tetraaryl-1,4-dihydropyridines

1,2,4,6-Tetraaryl-1,4-dihydropyridines were obtained by the one-pot reaction of chalcones and substituted anilines on the surface of Bi(III)nitrate-Al2O3. The reaction seems to proceed via β-oxygenation of Bi(III) enolised chalcones followed by Michael addition and heteroannulation with simultaneous retro aldol disproportionation. The presence of the ring-activating groups at ortho and para positions in the aniline seems to be essential for the reaction.Key words: 1,2,4,6-tetraryl-1,4-dihydropyridines, chalcones, substituted anilines, Bi(III) nitrate-alumina catalyst.

A new and convenient one-pot solid supported synthesis of 2,4,6-triarylpyridines

A new, convenient, efficient and cost-effective one-pot solid supported synthesis of 2,4,6-triarylpyridines from benzylideneacetophenones and urea, thiourea or their derivatives, using Bi(III) nitrate–Al 2O 3 is described. The reaction seems to proceed via β-oxygenation of Bi(III)-enolized benzylideneacetophenone followed by Michael addition, heteroannulation with simultaneous retro aldol disproportionation and subsequent catalytic oxidation and dehydration.