Materials & Chemicals : Synthesis


Boron- and Nitride-Containing Catalysts for Oxidative Dehydrogenation of Small Alkanes and Oxidative Coupling of Methane

UW–Madison researchers have developed improved ODH catalysts for converting short chain alkanes to desired olefins (e.g., propane to propene and ethene) with unprecedented selectivity (>90 percent).

The new catalysts contain boron and/or nitride and minimize unwanted byproducts including CO and CO2. They contain no precious metals, reduce the required temperature of the reaction and remain active for extended periods of time with no need for costly regenerative treatment.

In addition to driving ODH reactions, the new catalysts can be used to produce ethane or ethene via oxidative coupling of methane (OCM).

“Green” Catalytic Systems for Solvent-Free Alcohol Oxidations

Research from the University of Wisconsin-La Crosse has led to the discovery and development of a novel suite of catalytic systems for industrially-relevant green oxidations including the oxidative conversion of primary and secondary alcohols to value-added aldehydes and ketones. Similar systems have been developed for the oxidation of olefins to produce important epoxides, and for the oxidation of alkanes to produce alcohols. Specifically the team has developed a series of iron-based catalysts known as ‘helmet’ phthalocyaninaoto complexes of iron(III). Preliminary studies have focused on the use of what is commonly referred to as the ‘diiPc’ iron(III) system. Notably, the team has shown that this system is capable of catalytically oxidizing a diverse array of substrates including five non-benzylic alcohols (1-pentanol, 2-pentanol and cyclohexanol as well as 2,4-dimethyl-3-pentanol and 5-hydroxymethylfurfural) in the absence of added organic solvent. The presence of water as the monodentate axial ligand in the diiPc complex allows for markedly increased solubility in non-aromatic alcohols, making it an ideal catalyst for use with a much wider and more diverse range of substrates under solvent free conditions. It is envisaged that modification of the diiPc and related ligands will be undertaken to impart further enhancements to catalyst solubility in substrates or water, and/or superior stability in substrate alcohols. In addition to the diiPc system, the team have also developed a means of forming derivatized catalysts utilizing what is commonly referred to as a “helmet naphthalocyaninato” iron(III) complex. Specifically, a sulfonated version has been produced that possesses excellent solubility in water due to the added hydrophilic groups. To date, the sulfonated helmet naphthalocyaninato complex has been shown to provide for efficient formation of acetone from isopropanol as well as conversion of 2-pentanol to 2-pentanone using hydrogen peroxide as the primary oxidant. As such we anticipate that the same system would also be effective in the oxidation of 2-butanol to produce methyl ethyl ketone (MEK), an important commodity scale industrial chemical, and in many other commercially important transformations. Furthermore, preliminary studies have shown this molecule can be immobilized on various solid supports including anion-exchange resins, thereby resulting in a heterogeneous catalyst that can be utilized in the development of catalytic transformations that occur under flow conditions. Additionally, we now know that the sulfonated catalyst efficiently catalyzes the oxidation of phenol with hydrogen peroxide to produce para-benzoquinone. This transformation, along with other related reactions, is very important in the treatment of wastewater.

New Compounds for Treating High Blood Cholesterol and More

UW–Madison researchers have now developed a method using a rhodium-containing catalyst to make indole compounds, specifically cyclopropyl indoles and cyclohepta[b] indoles. The compounds may be developed into new pharmaceuticals to treat a variety of conditions.

Synthesizing Natural Products to Treat High Blood Cholesterol

UW–Madison researchers have developed an efficient method to synthesize indole compounds, specifically polysubstituted dimeric indoles. These compounds have potential health benefits because they are able to reduce the amount of PCSK9 in cells. PCSK9 is an enzyme known to play a major role in controlling the concentration of LDL cholesterol in the bloodstream.

Some of the compounds have been tested in vitro for their ability to increase the secretion of a potent blood sugar hormone in the body called glucagon-like peptide 1 (GLP-1). Others have the ability to selectively inhibit the secretion of interleukin-17 (IL-17), which is essential in many autoimmune diseases including arthritis, multiple sclerosis, psoriasis and inflammatory bowel disease.

The synthesis process involves a cascade reaction with transition metal catalysts. The resulting compounds can be further functionalized to yield more substituted indoles.

More Stable, Efficient Photocatalysts for Reducing Small Molecules

The researchers have now developed amino-terminated diamond surfaces that can be used as electron emitters for catalyzing the reduction of small molecules, particularly inert gases. Compared to the previously designed H-terminated diamond surfaces, the amino-terminated surfaces exhibit superior electron emission and are significantly more chemically stable in the presence of UV light and water.

Reduction reactions that can be carried out using the new photocatalyst include but are not limited to: N2 to NH3 or hydrazine (N2H4); CO2 to CO or organic molecules such as methane (CH4), formaldehyde (H2CO) or methanol (CH3OH); and the reduction of nitrogen oxides (NOx) to N2. Other molecules that can be reduced include benzene ring-containing organic molecules such as substituted and unsubstituted benzene and naphthalene.

Palladium-Based Catalysts Herald Greater Efficiency of Alcohol Oxidation to Esters and Acids

Utilizing heterogeneous palladium-based catalysts with co-catalysts such as tellurium or bismuth, UW–Madison researchers have developed a new method for the efficient synthesis of esters and carboxylic acids from organic alcohols.

To form an ester, an organic alcohol is reacted, in the presence of oxygen gas, with methanol or ethanol. The reaction occurs in the presence of the palladium-based catalyst and the co-catalyst. To form an acid, water can be added to the reaction mix.

Gemini Surfactant LLC Membranes from Thiol-Ene Polymerizations

The researchers have now developed a new and highly efficient approach for synthesizing crosslinkable Gemini surfactants that can be turned into membranes featuring the desired gyroid morphology.

In the new method, an LLC structure is formed from a mixture containing the functionalized surfactants, a thiol-ene crosslinking agent and a polar solvent. Upon crosslinking, the lyotropic phase morphology is substantially retained.

Phosphine Ligands Made Cheaper, Better

UW–Madison researchers have developed methods for synthesizing novel classes of chiral phosphine ligands via enantioselective copper-catalyzed halogenation. The process is rapid and flexible, and also can be used to streamline the preparation of known phosphines.

The researchers previously described their ‘recycling’ method for use with aromatic compounds. Now, they have rendered the process enantioselective using an asymmetric bidentate phosphine ligand to produce scaffolds with high enantiomeric purity.

In essence, the use of the phosphine ligand helps form a chiral center in a complex product that is otherwise costly or impossible to create.

New Peptide-Mimicking Compounds for Anti-Cancer PET Imaging

UW–Madison and USF researchers have developed a new class of RGD mimetic compounds called γ-AApeptides that specifically target tumor integrin αvβ3 and resist being degraded. The γ-AApeptide tracers mimic the structural and functional properties of natural peptide-based tracers but with significantly improved stability.

Selective Conversion of Lignin into Simple Aromatic Compounds

UW–Madison researchers have developed a metal-free, aerobic oxidation method that selectively transforms the benzylic alcohol in lignin to the corresponding ketone. The process uses a nitric acid (HNO3) catalyst combined with another Brønsted acid. The reaction leaves unchanged at least a portion of unprotected primary aliphatic alcohols in the lignin or lignin subunit.

The reaction may be carried out in any suitable polar solvent and in the presence of additional reagents including TEMPO and derivatives.

Crosslinkable Gemini Dicarboxylate Surfactant LLCs and Their Membranes

UW–Madison researchers have built on their previous work to efficiently synthesize crosslinkable Gemini surfactants that adopt bicontinuous cubic phases, including the gyroid phase. By incorporation of a photoinitiator into the hydrophobic domains of the LLC, the assembly can be crosslinked with retention of the gyroid structure.

Easier, More Flexible Synthesis of Therapeutic and Promising Compounds

UW–Madison researchers have developed efficient processes to prepare asymmetric, heteroatom-bearing stereotriads and tetrads via allene oxidation. The number and type of heteroatoms stereoselectively introduced into the hydrocarbon chain or ring is flexible, and the methods allow for the transfer of chirality to three new carbon-heteroatom bonds. The new triads and tetrads may be incorporated into biologically active molecules, including modified aminoglycoside and neuraminidase inhibitors.

Any reaction products can be further oxidized, reduced or hydrolyzed to form other compounds and intermediates, notably synthetic motifs containing three contiguous carbon-heteroatom bonds. Bicyclic methylene aziridines can be formed and altered to provide therapeutically-promising N,N-aminals in a one pot reaction.

Streamlined Scheduling for Large-Scale Chemical Production

UW–Madison researchers have developed a new propagation algorithm to accelerate the solution of MIP models for chemical production scheduling. Based on equipment and material limitations, the algorithm estimates the number of batches and the amount of materials that should be processed in order to meet customer demand. These estimates are used to constrain the search space of the MIP model, leading to dramatic computational improvements.

High-Symmetry, Bicontinuous Lyotropic Liquid Crystals with Percolating Nanoscale Domains

UW–Madison researchers have developed a new class of anionic Gemini amphiphiles based on aliphatic carboxylic acids that exhibit a strong propensity to form G-phase LLC assemblies in an aqueous solution. Moreover, these G-phases are broadly stable between 25 and 100 degrees Celsius and across a wide range of amphiphile concentrations (up to 20 weight percent).

The LLC-forming material comprises water or another polar solvent and an anionic Gemini (“twin tail”) surfactant containing at least one carboxylate moiety. This scaffold furnishes ready access to useful, high-symmetry Q-phase LLCs having well-defined pore wall functionalities that can be readily tuned by chemical synthesis for specific applications.

Improved Photocatalyst for Reducing Small Molecules

UW–Madison researchers have developed a reaction system and method for the photoreduction of molecules that uses diamonds with a negative electron affinity as the photocatalyst. The method involves illuminating a fluid sample containing the molecules to be reduced and a hydrogen surface-terminated diamond having a negative electron affinity. The illuminating light wavelength induces the emission of electrons from the diamond directly into the fluid sample. These emitted electrons induce the reduction of the molecules, forming a reduction product. The product then can be separated from the fluid sample and collected. This method can be used to reduce a variety of molecules, including small molecules such as N2, CO2, CO or NOx and aromatic molecules that include one or more benzene rings.

Generating Medical Isotopes with Safer Vessel and Materials

Wisconsin researchers have developed a ring-shaped, or annular, fissile solution vessel for generating medical isotopes.

The assembly holds three nested chambers. Ions are first directed into an internal target chamber containing a gas. The neutrons that are generated pass outward, through a cooling jacket, into the surrounding fissile solution vessel. This vessel contains an aqueous composition of nuclear material and is shaped to increase heat transfer area to volume. Neutrons strike the nuclear material, generating isotopes and additional neutrons. The solution vessel is separated by another cooling jacket from an outer chamber that reflects neutrons.

Synthesis of Endoperoxide from a Diene and Molecular Oxygen in the Presence of a Photocatalyst

UW–Madison researchers have developed a method of making an endoperoxide by reacting a diene and molecular oxygen in the presence of a metal photocatalyst with an excited state lifetime of at least 100 nanoseconds. In one embodiment, the catalyst is a Ruthenium-based photocatalyst. This method uses visible light and can produce good yields of endoperoxide.

Treating Pulmonary Disorders with Artificial Lung Surfactant

UW–Madison researchers and others have developed new artificial lung surfactants that mimic the SP-B protein. The materials are based on sequence-random copolymers that contain cationic and lipophilic subunits and are members of the nylon-3 family. They are prepared by ring-opening polymerization of beta-lactams. Also, N-terminal units can be attached to the copolymers to mimic surface tension properties exhibited by the SP-C protein.

Method to Produce Sorbic Acid and Pentadiene from Renewable Biostock

UW–Madison researchers have developed a method of making 2,4-hexadienoic acid (i.e., sorbic acid) and 1,3-pentadiene (i.e., piperylene) via an acid-catalyzed ring-opening of 6-methyl-5,6-dihydro-2-pyrone (i.e., parasorbic acid). The parasorbic acid can be made from a renewable precursor, 4-hydroxy-6-methyl-2-pyrone (HMP).

The method comprises converting a renewable feedstock, HMP, into parasorbic acid (PSA), and then opening the ring of the PSA by contacting the PSA with a solid acid catalyst. This can be performed with acid-catalyzed ring-opening to yield sorbic acid or with decarboxylation of the opened ring to yield pentadiene. The conversion of HMP to PSA is accomplished by hydrogenating the HMP in the presence of a catalyst comprising one or more noble metals. The conversion takes place in a solvent selected from the group of C1- to C6-alcohols and C1- to C6-carboxylic acids, and the ring-opening reactions take place in a polar, aprotic solvent or a mixed solvent of water and a polar, aprotic solvent.

A more specific, three-step approach begins by hydrogenating 4-hydroxy-6-methyl-2-pyrone (HMP) to yield 4-hydroxy-6-methyltetrahydro-2-pyrone (4-HMTHP). Then, the 4-HMTHP is dehydrated by contacting it with a solid acid catalyst to yield parasorbic acid. Finally, the ring of the PSA is opened by contacting the PSA with a solid acid catalyst to yield sorbic acid or pentadiene.

Pure, Cyclically-Constrained Gamma-Amino Acids for Medicine and Materials

UW–Madison researchers have now developed novel methods for producing cyclically-constrained γ-amino acids that are chiral and highly stereoselective. The researchers also have developed new compositions of cyclically-constrained γ-amino acid residues and reaction intermediates. The methods rely on a reaction that involves the Michael addition of an aldehyde to a cyclic nitroalkene. Oligomers containing the resulting γ-amino acid residues adopt specific conformations and can be used as scaffolds for the construction of biomedically active molecules. These methods provide access to new types of γ-amino acids.

Producing Methyl Vinyl Ketone from Levulinic Acid

UW–Madison researchers have developed an efficient method to convert levulinic acid to methyl vinyl ketone. The method involves performing a reaction with an aqueous solution comprising levulinic acid over an acid catalyst, preferably a solid acid catalyst, at a temperature from 500 to about 900 Kelvin and without added molecular hydrogen.  The reaction can be performed in either a batch or continuous reactor, although a continuous reactor is preferred. The reaction produces methyl vinyl ketone at higher yields from less expensive starting material compared to current methods.

Simple, Gentle and Chemoselective Method of Synthesizing Diazo Compounds

UW–Madison researchers have discovered a simpler way to make diazo compounds.  They found that the Staudinger reagent removes a nitrogen from an azido group.  Specifically, the diazo compounds can be prepared by reacting a tertiary phosphine carrying a reactive carbonyl group, which is of the type used in Staudinger ligation, with an azide.

Traceless Staudinger Ligation for the Synthesis of Peptides and Proteins in Water

UW–Madison researchers have discovered that the traceless Staudinger ligation can be achieved in water with a water-soluble reagent such as bis(p-dimethylaminoethylphenyl)phosphinomethanethiol.  This discovery enables the formation of an amide bond in a physiological setting.  It integrates traceless Staudinger ligation with expressed protein ligation, thus extending the reach of modern protein chemistry.

Efficient Method of Synthesizing Gamma2-Amino Acids for Applications in Medicine, Materials, Healthcare

UW-Madison researchers have developed novel compounds and methods for synthesizing γ2-amino acids and related products.  The highly efficient and enantioselective methods are based on Michael reactions of aldehydes with highly reactive nitroethylene.  The reactions are catalyzed by small amounts of readily prepared chiral pyrrolidines in the presence of commercially available and inexpensive carboxylic acids as cocatalysts.  The Michael products, α-substituted-γ-nitrobutyl aldehydes, are valuable building blocks for organic synthesis and can be converted to γ2-amino acids and their derivatives. 

Fast and Efficient Catalytic Metathesis of Secondary Amides for the Synthesis of Novel Molecules

UW-Madison researchers now have developed a different approach that allows catalytic transamidation and amide metathesis reactions to occur efficiently, quickly and at low temperatures. This approach uses imides to initiate the reactions. 

Specifically, this method involves reacting two or more distinct secondary amides in an aprotic solvent in the presence of a Bronsted base and an imide initiator. During the reaction, an acyl group exchange occurs between the secondary amides.

Iron Catalyst for Selective Hydrogenation of Aldehydes, Ketones and Imines

UW-Madison researchers have developed a method of using an iron-based, ligand-metal bifunctional catalyst for the selective hydrogenation of aldehydes, ketones and imines under mild conditions. This catalyst contains relatively inexpensive iron, rather than precious metals. When exposed to an aldehyde, ketone or imine, particularly in the presence of hydrogen gas, it facilitates a reduction reaction that is an important step in the production of pharmaceuticals, animal health products, agrochemicals, fungicides, pheromones, flavors and fragrances.

Efficient Beta2-Amino Acid Synthesis Via Organocatalytic Aldehyde Aminomethylationlation

UW-Madison researchers have developed an efficient method for the synthesis of beta2 amino acids. The method is based on an asymmetric aldehyde aminomethylation that involves a Mannich reaction between an aldehyde, a formaldehyde-derived iminium ion, and an organic catalyst.

Converting Biomass-Derived Carbohydrates to High-Quality, Long-Chain Liquid Fuels

UW-Madison researchers have developed a practical and energy-efficient catalytic process for producing high-quality, long-chain liquid fuels from carbohydrates. The multi-stage process uses combinations of self- and crossed-aldol condensation reactions, dehydration reactions and hydrogenation reactions to yield alkane, alkene and ether products.

Preferably, this process starts with an acid-catalyzed dehydration of biomass-derived carbohydrates. Then an aqueous-phase aldol condensation reaction yields large organic compounds, which are converted into long-chain alkanes via dehydration and/or hydrogenation. The aldol condensation reaction takes place in the presence of a stable, recyclable and solid-base catalyst, which is comprised of magnesium, zirconium, oxygen and possibly palladium.

Method for Synthesizing Beta-Polypeptides from Functionalized Beta-Lactam Monomers

UW-Madison researchers have developed a robust method for making large quantities of poly-beta-peptides under mild and controllable conditions. The method involves polymerizing beta-lactams in an organic solvent. At least one of the monomers may comprise a fused, bicyclic beta-lactam moiety. A base initiator and a non-metal-containing co-initiator, such as an anhydride, are also present. This process was successfully used to synthesize a series of beta-peptide homopolymers and co-polymers, many of which exhibited antimicrobial activity.

Systems and Methods for the Cyclotron Production of Iodine-124

UW-Madison researchers have developed an improved method for the cyclotron production of I-124 using an aluminum telluride (Al2Te3) target. The method involves producing I-124 from an isotopically enriched aluminum telluride target via the 124Te(p,n) or 124Te(d,2n) reaction. The I-124 formed during irradiation is sublimated from the target stock by dry distillation in a resistive furnace and then swept in a gas stream to a chilled quartz trap downstream. It may be delivered as a solid film on a quartz tube or extracted by scrubbing with a mild base for radio labeling.

Improved Asymmetric Hydroformylation of Therapeutics Using Novel Bisphosphines

UW–Madison researchers have developed a method for using a new class of bisphosphines as ligands in catalytic transformations of alkenes. The method involves subjecting an alkene to an asymmetric reaction such as hydroformylation, which is carried out in the presence of a bisphosphine ligand catalyst. The bisphosphine ligand is synthesized according to the formula depicted in the figure, or as the opposite enantiomer of the formula. Using this process, asymmetric hydroformylation reactions resulting in 90 percent or greater of the desired enantiomer are possible. The ligand structure has a modular design, which can be varied systematically to obtain the best results for any given alkene substrate, and can be synthesized efficiently from readily available raw materials.

Neoglycorandomization and Digitoxin Analogs

UW-Madison researchers have now developed a different approach to glycosylating natural compounds to create a large library of diverse compounds for high throughput screening. This approach, neoglycorandomization, uses a universal chemical glycosylation method that employs reducing sugars and requires no protection or activation. It is based on the chemoselective formation of glycosidic bonds between the reducing sugars and an aglycon with a secondary alkoxyamine.

To form a neoglycoside, the alkoxyamine-containing aglycon is reacted with at least one reducing sugar selected from the group consisting of L-sugars, D-sugars, amino-sugars, deoxy-sugars, dideoxy-sugars, glucose epimers, substituted sugars, uronic acids, and oligosaccharides.

Seven-Membered Heterocyclic Carbenes Coordinate with a Variety of Metals to Generate Chiral Metal Complexes

UW-Madison researchers have developed non-planar N-heterocyclic carbenes that are especially useful in asymmetric catalysis. These seven-membered carbenes have intrinsic chirality, making them naturally selective toward particular enantiomeric forms. They coordinate with a variety of metals to generate chiral metal complexes, which can be widely used in metal-catalyzed reactions for the synthesis of organic compounds, including those used in pharmaceutical compositions.

Methods for Ligating Molecules to Surfaces

UW-Madison researchers have now discovered that Staudinger ligation provides a rapid and efficient means to covalently attach proteins or other molecules to a specific site on a surface. The covalent ligation is based on the reaction of an azide and a phosphinothioester to form an amide bond. Preferably, a phosphinothioester is covalently bound to the surface through a linker group, and an azide functional group is attached to the molecule to be ligated. Alternatively, the azide group can be linked to the surface and the phosphinothioester can be attached to the molecule to be ligated. Next, the molecule to be immobilized is added to the surface so the phosphinothioester and the azide group can react to form an amide bond, covalently linking the molecule to the surface.

Diazaphosphacycles, Which Are Used to Catalyze Commercially Important Reactions, and Methods of Synthesis

UW–Madison researchers have developed diazaphosphacycles and methods for synthesizing them. They further developed transition metal complexes that include diazaphosphacycles and methods for using them in catalytic transformations. The method to synthesize a diazaphosphacycle includes reacting a phosphine with a diimine and optionally one or more equivalents of an acid halide, a sulfonyl halide, a phosphoryl halide or an acid anhydride in the substantial absence of O2 to form the diazaphosphacycle. The phosphine has the formula R1-PH2, where R1 is a substituted or unsubstituted aryl, alkyl, alkenyl, cycloalkyl or ferrocenyl group.

Catalytic Transamidation and Amide Metathesis under Moderate Conditions

UW-Madison researchers have developed a method of manipulating carboxamide-containing molecules by using low-temperature transamidation and amide metathesis reactions with a specified class of catalysts. The method includes low-temperature transamidation between or among amine and amide reactants, as well as low-temperature amide metathesis reactions between or among amide reactants. Amides are reacted with or without amines in the presence of various types of metal catalysts at a temperature of 250 degrees Celsius or less.

Heterogeneous Protein Foldamers Containing Alpha, Beta and Gamma Amino Acids

UW-Madison researchers have developed polypeptide foldamers containing alpha-amino acids along with cyclically constrained beta-amino acids and gamma-amino acids. These unnatural compounds contain rotationally constrained amino acid residues that are not amenable to enzymatic degradation, making them useful to probe protein-protein and other large molecule interactions. Because the backbone is heterogeneous, a portion of the residues, such as the alpha-amino acids, can provide functional diversity, while the cyclically constrained residues confer conformational specificity and stability.

Synthesis of Proteins and Peptides Selectively Modified by Sulfation, Phosphorylation or Glycosylation

UW–Madison researchers have developed methods that use a new protecting group strategy for the synthesis of proteins and peptides that are selectively modified by sulfation, phosphorylation and/or glycosylation. The methods use hydroxyl protecting groups with an azide moiety, which do not react under the conditions typically used in peptide synthesis, to create protected amino acids useful as building blocks for the synthesis of proteins or peptides. After synthesis, the amino acid residues can be selectively deprotected and modified.

Chemical Synthesis of Reagents for Peptide Coupling

UW-Madison researchers have developed improved methods for synthesizing phosphinothiol reagents. These synthesis techniques take advantage of phosphorus’s strong interaction with boron, and are based on an easily prepared alkylating agent and a commercially available borane-organophosphine complex. In the methods, the alkylating agent is reacted with the borane-organophosphine complex. Disrupting the resulting phosphine-borane complex and removing the protecting group generates the phosphinothiol reagents.

Low-Temperature Process to Produce Hydrocarbons from Oxygenated Substrates, Including Sugars

UW-Madison researchers have developed a method of producing hydrocarbons from oxygenated reactants such as glycerol, glucose or sorbitol. The method includes the steps of reacting water and a water-soluble oxygenated compound in the presence of a metal-containing catalyst. The reaction can take place in either the vapor phase or, preferably, in the condensed liquid phase. This method allows the production of hydrocarbons from oxygenated compounds ultimately derived from fully renewable plant biomass. 

Staudinger Ligation Method for Rapid and Reliable Chemical Synthesis of Proteins

UW-Madison researchers have developed an improved method of synthesizing proteins that does not require a cysteine residue at the ligation junction.  This method expands the utility of total protein synthesis by removing the limitation inherent in native chemical ligation and expressed protein ligation.  It is inspired by the Staudinger reaction, in which a phosphine molecule is used to reduce an azide to an amine. 

In this method, a phosphinothioester and an azide are united to form an amide bond.  A phosphinothiol reagent is used to efficiently generate a phosphinothioester from an amino acid, peptide or protein fragment.  An azido group then can be formed at the N-terminus or a basic side group of another amino acid, peptide or protein.  Then the phosphinothioester is reacted with the azido group to ligate the amino acids, peptides or proteins.

This reaction allows the formation of an amide bond among a wide variety of chemical species.  It can be used to repeatedly ligate natural and/or nonnatural amino acids to synthesize proteins or peptides.  Large peptides or proteins can be formed by ligating two or more small peptides or proteins.

Use of Glycorandomization to Produce Novel Glycosylated Products for Drug Discovery

A UW-Madison researcher has developed combinatorial methods for rapidly generating a diverse library of novel glycosylated compounds for use in drug discovery. Glycorandomization is a chemoenzymatic strategy that overcomes the limitations in natural product derivatization associated with both chemistry-based approaches and in vivo engineering.

In the methods, at least one aglycon and a pool of nucleoside diphosphate (NDP)-sugars are incubated with a glycosyltransferase enzyme to produce glycorandomized structures. The pool of NDP-sugars may include difficult-to-produce or never-before-produced sugars, which can now be made easily and efficiently through a one-step nucleotidyltransferase-catalyzed conversion developed by the inventors. The glycorandomized structures may be incubated with the sugars and glycosyltransferase multiple times to generate additional compounds. The glycorandomized structures may also be incubated with at least one chemoselectively ligatable moiety to generate chemoselectively-ligated compounds.

Low Temperature Hydrogen Fuel Production Using Renewable Starting Materials

UW-Madison researchers have developed a method to generate hydrogen fuel through low-temperature, catalytic steam reforming of oxygenated hydrocarbons, such as ethanediol, glycerol, sorbitol, glucose and ethanol. Unlike conventional starting materials for hydrogen production, which come from natural gas, oxygenated hydrocarbons can be derived from renewable resources, like plant biomass. Moreover, although the inventors’ method also produces carbon dioxide as a byproduct, the use of plant biomass should reduce the net release of CO2 to the atmosphere, because plants fix and store CO2 in their biomass during growth.

Silylenes and Germylenes for Catalysis of Olefin Polymerization

UW-Madison researchers have developed a method of using divalent silicon and germanium compounds to catalyze olefin polymerization reactions.  Specifically, the method uses a cyclic silylene or cyclic germylene in the presence of terminal alkene or alkyne monomers as a catalyst to synthesize olefin polymers.

One-Step Synthesis of Diazaphosphacycles

UW-Madison researchers have developed a relatively easy, one-step method of synthesizing a diazaphosphacycle. To generate a diazaphosphacycle, a phosphine is reacted with a diimine and one or more equivalents of an acid halide, a sulfonyl halide, a phosphoryl halide, or an acid anhydride, in the absence of oxygen. The phosphine has the formula R1-PH2, where R1 is a substituted or unsubstituted aryl, alkyl, alkenyl, cycloalkyl or ferrocenyl group.

Methods and Reagents for Capping Ruthenium or Osmium Carbene-Catalyzed ROMP Products

UW-Madison researchers have developed a method for the terminal attachment of functional groups to materials generated by ROMP. It involves preparing a telechelic polymer using a ruthenium or osmium carbene catalyst and a capping agent. More specifically, a monomer is polymerized in the presence of a ruthenium or osmium carbene catalyst to form a polymer template. Then the polymer template is combined with a functionalized capping agent under conditions for forming a terminally functionalized polymer.

Synthesis of Conjugated Essential Fatty Acids, Including CLA

UW–Madison researchers have developed a method of preparing select isomers of conjugated linoleic and linolenic acids under mild conditions. The technique can be used to produce and purify cis-9, trans-11, the CLA isomer believed to be most beneficial.

First, a superstrong base is used to remove protons from a polyunsaturated fatty acid that contains two or more double bonds in its hydrocarbon chain. Reprotonation by a strong acid then yields the desired conjugated isomers. Reaction with a selective lipase enzyme, which can discriminate between different isomers, purifies the yield.