The synthesis of α-hydroxy aldehydes and hydroxymethyl ketones as well as their interconversion t... more The synthesis of α-hydroxy aldehydes and hydroxymethyl ketones as well as their interconversion to each other are discussed in this thesis. The literature survey of the monograph reviews the synthetic methods for the preparation of 1,2-bifunctionalized hydroxy aldehydes and ketones. The keto-aldehyde isomerisation reaction catalyzed by Triosephosphate isomerase enzyme (TIM) and organic compounds that interact with the TIM are also introduced. In addition, the microwave heating techniques in organic syntheses are reviewed. The practical work consists of two entities: The synthesis of new substrate candidates and transition state analogues for a mutated monomeric TIM. These compounds are model compounds for the catalytic activity and the structural studies of the mutated monomeric TIM. The synthesis of the sulphonyl α-hydroxy ketone-based substrate candidates consists of four successive syntheses. The microwave-activation was utilized in the preparation of a carbon-sulphur bond and th...
The microwave-assisted synthesis of terminal α-hydroxy ketones from acid chlorides and tris(trime... more The microwave-assisted synthesis of terminal α-hydroxy ketones from acid chlorides and tris(trimethylsiloxy)ethylene in the presence of triethylamine is reported. The use of triethylamine had several advantages in the reaction: it increased the reactivity of the acid chloride, acted as a scavenger of the HCl that was produced in the reaction, protected the silylated enol from decomposition, and made the excess
An efficient, facile microwave-assisted synthesis has been developed for the preparation of unsym... more An efficient, facile microwave-assisted synthesis has been developed for the preparation of unsymmetrical sulfide derivatives from 3-mercaptopropionic acid and a wide variety of alkyl, allyl or aryl chlorides or bromides. The synthesis performed in ethanol at 80 or 120 °C using sodium hydroxide as a base, selectively without an offensive smell, generates 3-(alkylthio)propionic acids in good yields. Effects of reaction components, temperature, and the heating technique on the formation of the product and side-products were studied.
ABSTRACT IndPHOX (indole phosphine oxazoline) ligands were utilized in palladium-catalysed asymme... more ABSTRACT IndPHOX (indole phosphine oxazoline) ligands were utilized in palladium-catalysed asymmetric allylic amination with different N-nucleophiles. The reactions proceeded well and excellent enantioselectivities of up to 99% were achieved.
Powder-like extract of Ricinus communis seeds contain a toxic protein, ricin, which has a history... more Powder-like extract of Ricinus communis seeds contain a toxic protein, ricin, which has a history of military, criminal and terroristic use. As the detection of ricin in this "terrorist powder" is difficult and time-consuming, related low mass metabolites have been suggested to be useful for screening as biomarkers of ricin. To apply a comprehensive NMR-based analysis strategy for annotation, isolation and structure elucidation of low molecular weight plant metabolites of Ricinus communis seeds. The seed extract was prepared with a well-known acetone extraction approach. The common metabolites were annotated from seed extract dissolved in acidic solution using (1) H NMR spectroscopy with spectrum library comparison and standard addition, whereas unconfirmed metabolites were identified using multi-step off-line HPLC-DAD-NMR approach. In addition to the common plant metabolites, two previously unreported compounds, 1,3-digalactoinositol and ricinyl-alanine, were identified w...
IndPHOX (indole phosphine oxazoline) ligands were utilized in palladium-catalysed asymmetric ally... more IndPHOX (indole phosphine oxazoline) ligands were utilized in palladium-catalysed asymmetric allylic amination with different N-nucleophiles. The reactions proceeded well and excellent enantioselectivities of up to 99% were achieved.
A simple method for the asymmetric α-oxybenzoylation of aldehydes is presented. Treatment of a se... more A simple method for the asymmetric α-oxybenzoylation of aldehydes is presented. Treatment of a series of aldehydes with benzoyl peroxide in the presence of a MacMillan imidazolidinone leads directly to the α-oxybenzoylated product with excellent levels of asymmetric induction.
ABSTRACT Four indole-olefin-oxazoline (IndOlefOx) ligands were synthesized and evaluated in Rh-ca... more ABSTRACT Four indole-olefin-oxazoline (IndOlefOx) ligands were synthesized and evaluated in Rh-catalyzed reactions between organoboronics and a lactam or a lactone. In addition to the expected conjugate addition products, the formation of significant amounts of Heck-type products was observed. The scope and limitations of these reactions were investigated.
The microwave-assisted synthesis of terminal α-hydroxy ketones from acid chlorides and tris(trime... more The microwave-assisted synthesis of terminal α-hydroxy ketones from acid chlorides and tris(trimethylsiloxy)ethylene in the presence of triethylamine is reported. The use of triethylamine had several advantages in the reaction: it increased the reactivity of the acid chloride, acted as a scavenger of the HCl that was produced in the reaction, protected the silylated enol from decomposition, and made the excess
ABSTRACT N-Functionalized IndPHOX ligands bearing various groups have been synthesized and the ef... more ABSTRACT N-Functionalized IndPHOX ligands bearing various groups have been synthesized and the effects of the N1-substituent on the reaction rate, yield, and asymmetric induction in a palladium-catalyzed allylic substitution reaction are reported. The presence of an oxygen atom in the ligands, namely an N-MOM or N-THP group, led to enhancement of the enantioselectivity in the allylic amination reaction. In addition, a ligand with a chiral oxazoline ring at C-1 and a phosphane substituent at C-2 provided high enantioselectivity in good yield in an asymmetric allylic alkylation reaction.
Crystallographic binding studies have been carried out to probe the active-site binding propertie... more Crystallographic binding studies have been carried out to probe the active-site binding properties of a monomeric variant (A-TIM) of triosephosphate isomerase (TIM). These binding studies are part of a structure-based directed-evolution project aimed towards changing the substrate specificity of monomeric TIM and are therefore aimed at finding binders which are substrate-like molecules. A-TIM has a modified more extended binding pocket between loop-7 and loop-8 compared with wild-type TIM. The A-TIM crystals were grown in the presence of citrate, which is bound in the active site of each of the two molecules in the asymmetric unit. In this complex, the active-site loops loop-6 and loop-7 adopt the closed conformation, similar to that observed in liganded wild-type TIM. Extensive crystal-soaking protocols have been developed to flush the bound citrate out of the active-site pocket of both molecules and the crystal structure shows that the unliganded open conformation of the A-TIM active site is the same as in unliganded wild-type TIM. It is also shown that sulfonate compounds corresponding to the transition-state analogue 2-phosphoglycolate bind in the active site, which has a closed conformation. It is also shown that the new binding pocket of A-TIM can bind 3-phosphoglycerate (3PGA; an analogue of a C4-sugar phosphate) and 4-phospho-D-erythronohydroxamic acid (4PEH; an analogue of a C5-sugar phosphate). Therefore, these studies have provided a rationale for starting directed-evolution experiments aimed at generating the catalytic properties of a C5-sugar phosphate isomerase on the A-TIM framework.
The synthesis of α-hydroxy aldehydes and hydroxymethyl ketones as well as their interconversion t... more The synthesis of α-hydroxy aldehydes and hydroxymethyl ketones as well as their interconversion to each other are discussed in this thesis. The literature survey of the monograph reviews the synthetic methods for the preparation of 1,2-bifunctionalized hydroxy aldehydes and ketones. The keto-aldehyde isomerisation reaction catalyzed by Triosephosphate isomerase enzyme (TIM) and organic compounds that interact with the TIM are also introduced. In addition, the microwave heating techniques in organic syntheses are reviewed. The practical work consists of two entities: The synthesis of new substrate candidates and transition state analogues for a mutated monomeric TIM. These compounds are model compounds for the catalytic activity and the structural studies of the mutated monomeric TIM. The synthesis of the sulphonyl α-hydroxy ketone-based substrate candidates consists of four successive syntheses. The microwave-activation was utilized in the preparation of a carbon-sulphur bond and th...
The microwave-assisted synthesis of terminal α-hydroxy ketones from acid chlorides and tris(trime... more The microwave-assisted synthesis of terminal α-hydroxy ketones from acid chlorides and tris(trimethylsiloxy)ethylene in the presence of triethylamine is reported. The use of triethylamine had several advantages in the reaction: it increased the reactivity of the acid chloride, acted as a scavenger of the HCl that was produced in the reaction, protected the silylated enol from decomposition, and made the excess
An efficient, facile microwave-assisted synthesis has been developed for the preparation of unsym... more An efficient, facile microwave-assisted synthesis has been developed for the preparation of unsymmetrical sulfide derivatives from 3-mercaptopropionic acid and a wide variety of alkyl, allyl or aryl chlorides or bromides. The synthesis performed in ethanol at 80 or 120 °C using sodium hydroxide as a base, selectively without an offensive smell, generates 3-(alkylthio)propionic acids in good yields. Effects of reaction components, temperature, and the heating technique on the formation of the product and side-products were studied.
ABSTRACT IndPHOX (indole phosphine oxazoline) ligands were utilized in palladium-catalysed asymme... more ABSTRACT IndPHOX (indole phosphine oxazoline) ligands were utilized in palladium-catalysed asymmetric allylic amination with different N-nucleophiles. The reactions proceeded well and excellent enantioselectivities of up to 99% were achieved.
Powder-like extract of Ricinus communis seeds contain a toxic protein, ricin, which has a history... more Powder-like extract of Ricinus communis seeds contain a toxic protein, ricin, which has a history of military, criminal and terroristic use. As the detection of ricin in this "terrorist powder" is difficult and time-consuming, related low mass metabolites have been suggested to be useful for screening as biomarkers of ricin. To apply a comprehensive NMR-based analysis strategy for annotation, isolation and structure elucidation of low molecular weight plant metabolites of Ricinus communis seeds. The seed extract was prepared with a well-known acetone extraction approach. The common metabolites were annotated from seed extract dissolved in acidic solution using (1) H NMR spectroscopy with spectrum library comparison and standard addition, whereas unconfirmed metabolites were identified using multi-step off-line HPLC-DAD-NMR approach. In addition to the common plant metabolites, two previously unreported compounds, 1,3-digalactoinositol and ricinyl-alanine, were identified w...
IndPHOX (indole phosphine oxazoline) ligands were utilized in palladium-catalysed asymmetric ally... more IndPHOX (indole phosphine oxazoline) ligands were utilized in palladium-catalysed asymmetric allylic amination with different N-nucleophiles. The reactions proceeded well and excellent enantioselectivities of up to 99% were achieved.
A simple method for the asymmetric α-oxybenzoylation of aldehydes is presented. Treatment of a se... more A simple method for the asymmetric α-oxybenzoylation of aldehydes is presented. Treatment of a series of aldehydes with benzoyl peroxide in the presence of a MacMillan imidazolidinone leads directly to the α-oxybenzoylated product with excellent levels of asymmetric induction.
ABSTRACT Four indole-olefin-oxazoline (IndOlefOx) ligands were synthesized and evaluated in Rh-ca... more ABSTRACT Four indole-olefin-oxazoline (IndOlefOx) ligands were synthesized and evaluated in Rh-catalyzed reactions between organoboronics and a lactam or a lactone. In addition to the expected conjugate addition products, the formation of significant amounts of Heck-type products was observed. The scope and limitations of these reactions were investigated.
The microwave-assisted synthesis of terminal α-hydroxy ketones from acid chlorides and tris(trime... more The microwave-assisted synthesis of terminal α-hydroxy ketones from acid chlorides and tris(trimethylsiloxy)ethylene in the presence of triethylamine is reported. The use of triethylamine had several advantages in the reaction: it increased the reactivity of the acid chloride, acted as a scavenger of the HCl that was produced in the reaction, protected the silylated enol from decomposition, and made the excess
ABSTRACT N-Functionalized IndPHOX ligands bearing various groups have been synthesized and the ef... more ABSTRACT N-Functionalized IndPHOX ligands bearing various groups have been synthesized and the effects of the N1-substituent on the reaction rate, yield, and asymmetric induction in a palladium-catalyzed allylic substitution reaction are reported. The presence of an oxygen atom in the ligands, namely an N-MOM or N-THP group, led to enhancement of the enantioselectivity in the allylic amination reaction. In addition, a ligand with a chiral oxazoline ring at C-1 and a phosphane substituent at C-2 provided high enantioselectivity in good yield in an asymmetric allylic alkylation reaction.
Crystallographic binding studies have been carried out to probe the active-site binding propertie... more Crystallographic binding studies have been carried out to probe the active-site binding properties of a monomeric variant (A-TIM) of triosephosphate isomerase (TIM). These binding studies are part of a structure-based directed-evolution project aimed towards changing the substrate specificity of monomeric TIM and are therefore aimed at finding binders which are substrate-like molecules. A-TIM has a modified more extended binding pocket between loop-7 and loop-8 compared with wild-type TIM. The A-TIM crystals were grown in the presence of citrate, which is bound in the active site of each of the two molecules in the asymmetric unit. In this complex, the active-site loops loop-6 and loop-7 adopt the closed conformation, similar to that observed in liganded wild-type TIM. Extensive crystal-soaking protocols have been developed to flush the bound citrate out of the active-site pocket of both molecules and the crystal structure shows that the unliganded open conformation of the A-TIM active site is the same as in unliganded wild-type TIM. It is also shown that sulfonate compounds corresponding to the transition-state analogue 2-phosphoglycolate bind in the active site, which has a closed conformation. It is also shown that the new binding pocket of A-TIM can bind 3-phosphoglycerate (3PGA; an analogue of a C4-sugar phosphate) and 4-phospho-D-erythronohydroxamic acid (4PEH; an analogue of a C5-sugar phosphate). Therefore, these studies have provided a rationale for starting directed-evolution experiments aimed at generating the catalytic properties of a C5-sugar phosphate isomerase on the A-TIM framework.
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