The mechanism of the Ru(arene)(amino alcohol)-catalyzed transfer hydrogenation of ketones using isopropyl alcohol as the hydrogen source has been studied by means of hybrid density functional methods (B3PW91). Three mechanistic alternatives were evaluated, and it was shown that the reaction takes place via a six-membered transition state, where a metal-bound hydride and a proton of a coordinated amine are transferred simultaneously to the ketone. Further calculations provided a general rationale for the rate of the reaction by comparison of steric effects in the ground and transition states of the ruthenium hydride complex. It was found that the TS has a strong preference for planarity, and this in turn is dependent on the conformational behavior of the O,N-linkage of the amino alcohol ligand. Finally, a general model, rationalizing the enantioselectivity of the reaction, was developed. Experimental studies of both rate and enantioselectivity were used in order to support the computational results.

Optically active 5(4H)-oxazolones have been synthesized from L-tryptophan and an excess of trifluoro-, trichloro-, and dichloroacetic anhydrides. Some of the 5(4H)-xazolones have been further transformed to the isomeric 5(2H)-oxazolones as well as oxazolones with exocyclic double bonds. Treatment of the various oxazolones under hydrolytic, acidic and Friedel-Crafts acylation conditions gave indole-3-pyruvic acid, alpha,beta-dehydrotryptophans, beta-carbolines as well as the functionalized cyclopentanoindole 32. Treatment of the 4-(3-indolylmethyl)-2-trifluoromethyl-5(2H)-oxazolone (17) with trifluoroacetic acid gave the 3,4-bridged azepinoindole 35.

The poly(dimethylsiloxane) (PDMS) material provides a number of advantageous features, such as flexibility, elasticity, and transparency, making it useful in integrated analytical systems. Hard fused-silica capillary structures and soft PDMS channels can easily be combined by a tight fit, which offers many alternatives for structure combinations. PDMS and fused silica are in different ways prone to adsorption of low levels of organic compounds. The need for modification of the inner wall surface of PDMS channels may often be necessary, and in this paper, we describe an easy and effective method using the amine-containing polymer PolyE-323 to deactivate both fused-silica and PDMS surfaces. The adsorption of selected peptides to untreated surfaces was compared to PolyE-323-modified surfaces, using both radionuclide imaging and capillary electrophoresis experiments. The polyamine modification displayed a substantially reduced adsorption of three hydrophobic test peptides compared to the native PDMS surface. Filling and storage of aqueous solution were also possible in PolyE-323-modified PDMS channels. In addition, hybrid microstructures of fused silica and PDMS could simultaneously be deactivated in one simple coating procedure.

Five-membered rings are readily prepared by 5-exo-trig radical cyclization. This thesis is concerned with novel methodology for pyrrolidine synthesis. We have synthesised selenium containing radical precursors from aziridines and α-phenylseleno ketones, and cyclized them to 2,4- and 3,4-disubstituted pyrrolidines. A few examples of 5-exo-dig cyclization were also demonstrated. In another study we investigated the capacity of the nitrogen protecting group to direct diastereoselectivity in the formation of 2,4-disubstituted pyrrolidines. The diphenylphosphinoyl protecting group directed cyclization to occur in a highly cis-selective manner. When cyclizations were performed at 17 ^oC, cis/trans-ratios as high as 24/1 were obtained. In contrast, cyclization of the unprotected pyrrolidine precursor afforded the trans-diastereomer as the major product (cis/trans = 1/3.3 – 1/20). We also examined the use of a hydroxyl auxiliary for controlling diastereoselectivity in radical cyclization. The required selenium containing radical precursors were synthesised from 2-cyanoaziridines by addition of organometallic reagents, reduction of the resulting aziridine ketone, and benzeneselenol ring-opening of the aziridine. Cyclization at 17 ^oC produced 2,4-disubstituted pyrrolidines substantially enriched in the trans-isomer (cis/trans = 1/9 – 1/12). Novel radical cyclization approaches to thiazolines and pyrrolines were also tried.

The thesis also describes attempts to improve the Hassner aziridine synthesis by employing stannous chloride as a functional group tolerant reducing agent.

Total syntheses of (+/-)-alpha-and (+/-)-gamma-lycorane are described. The key steps in the syntheses are the stereocontrolled palladium-catalyzed intramolecular 1,4-chloroamidation of 12 to 13 and the subsequent anti-stereoselective copper-catalyzed S(N)2' reaction of allylic chloride 13 with [3,4-(methylenedioxy)phenyl]magnesium bromide to give 14. Hexahydroindole 14 has the required relative stereochemistry between carbons 3a, 7, and 7a for alpha-lycorane (1a) and was transformed to the latter via 15 and 16. The epimeric gamma-lycorane (2) was obtained by performing the Bischler-Napieralski cyclization on 14, which led to a highly stereoselective isomerization to give exclusively 17. Compound 17 was subsequently transformed to 2. The overall yield from ester 8 to (+/-)-alpha- and (+/-)-gamma-lycorane was 40 and 36%, respectively.

The research described in this thesis is directed toward the efficient, enantioselective synthesis of chiral products that have useful functionality. This goal was pursued through catalytic asymmetric hydrogenation, a reaction class that selectively introduces one or two stereocenters into a molecule in an atom-efficient step. This reaction uses a small amount (often <1 mol%) of a chiral catalyst to impart stereoselectivity to the product formed. Though catalytic asymmetric hydrogenation is not a new reaction type, there remain many substrate classes for which it is ineffective. The present thesis describes efforts to extend the reaction to some of these substrates classes. Some of the products synthesized in these studies may eventually find use as building blocks for the production of chiral pharmaceuticals, agrochemicals, or flavouring or colouring agents. However, the primary and immediate aim of this thesis was to develop and demonstrate new catalysts that are rapid and effective in the asymmetric hydrogenation of a broad range of compounds.

Paper I describes the design and construction of two new, related chiral iridium compounds that are catalysts for asymmetric hydrogenation. They each contain an N,P-donating phosphinooxazoline ligand that is held together by a rigid bicyclic unit. One of these iridium compounds catalyzed the asymmetric hydrogenation of acyclic aryl imines, often with very good enantioselectivities. This is particularly notable because acyclic imines are difficult to reduce with useful enantioselectivity. The second catalyst was useful for the asymmetric hydrogenation of two aryl olefins. In Paper II, the class of catalysts introduced into Paper I is expanded to include many more related compounds, and these are also applied to the asymmetric hydrogenation of prochiral imines and olefins. By studying a range of related catalysts that differ in a single attribute, we were able to probe how different parts of the catalyst affect the yield and selectivity of the hydrogenation reactions.

Whereas iridium catalysts had been applied to the asymmetric hydrogenation of imines and largely unfunctionalized olefins prior to this work (with varied degrees of success), they had not been used to reduce fluoroolefins. Their hydrogenation, which is discussed in Paper III, was complicated by concomitant defluorination to yield non-halogenated alkanes. To combat this problem, several iridium-based hydrogenation catalysts were applied to the reaction. Two catalysts stood out for their ability to produce chiral fluoroalkanes in good enantioselectivity while minimizing the defluorination reaction, and one of these bore a phosphinooxazoline ligand of the type described in Papers I and II.

Enol phosphinates are another class of olefins that had not previously been subjected to iridium-catalyzed asymmetric hydrogenation. They do, however, constitute an attractive substrate class, because the product chiral alkyl phosphinates can be transformed into chiral alcohols or chiral phosphines with no erosion of enantiopurity. Iridium complexes of the phosphinooxazoline ligands described in Papers I and II were extremely effective catalysts for the asymmetric hydrogenation of enol phosphinates. They produced alkyl phosphinates from di- and trisubstituted enol phosphinate, β-ketoester-derived enol phosphinates, and even purely alkyl-substituted enol phopshinates, in very high yields and enantioselectivities.

The thioredoxins are small ubiquitous redox proteins with the conserved redox catalytic sequence-Trp-Cys-Gly-Pro-Cys-Lys, where the Cys residues undergo reversible NADPH dependent reduction by selenocysteine containing flavoprotein thioredoxin reductases. Thioredoxin expression is increased in several human primary cancers including lung, colon, cervix, liver, pancreatic, colorectal and squamous cell cancer. The thioredoxin/thioredoxin reductase pathway therefore provides an attractive target for cancer drug development. Organotellurium steroid, lipid, amino acid, nucleic base, and polyamine inhibitors were synthesized on the basis that they might be selectively or differentially incorporated into tumor cells. Some of the newly prepared classes of tellurium-based inhibitors (lipid-like compounds 3b and 3e, amino acid derivative 5b, nucleic base derivative 8b, and polyamine derivatives 14a and 14b) inhibited TrxR/Trx and cancer cell growth in culture with IC(50) values in the low micromolar range.

Thioredoxin (Trx) expression is increased in several human primary cancers associated with aggressive tumor growth and decreased patient survival, and the Trx/Trx reductase (TrxR) system therefore provides an attractive target for cancer drug development. Various gold(III) compounds with none, one, two or three carbon-gold bonds were evaluated for their capacity to inhibit TrxR and the growth of MCF-7 cancer cells in vitro. Compounds with up to two carbon-gold bonds were often potent inhibitors of TrxR with IC50 values as low as 2 nmol/l. In the presence of Trx and insulin the inhibiting capacity was much lower. However, the inhibitory concentrations of the compounds did not correlate with the ability to kill cells. Out of the organometallics tested, only compound 8 with two carbon-gold bonds was able to inhibit colony formation by MCF-7 breast cancer cells at low micromolar concentrations (IC50=1,6umol/l). Unfortunately, the compound did not show any anti-tumor activity against MCF-7 breast cancer and HT-29 colon cancer zenografts in scid mice.

Peptide secondary structure mimetics are important tools in medicinal chemistry, as they provide analogues of endogeneous peptides with new physicochemical and pharmacological properties. The β-hairpin motif has been shown to be involved in numerous physiological processes, among others in regulation of eucariotic gene transcription. This thesis addresses the design, synthesis and conformational analysis of photoswitchable β-hairpin mimetics.

The developmental work included the establishment of an improved procedure for cross coupling of aryl halides with terminal alkynes. Microwave mediated Sonogashira couplings in closed vessels were optimized under homogeneous and solid-phase conditions furnishing excellent yields for a large variety of substrates within 5 – 25 minutes. In addition, microwave heating was shown not to have any non-conventional effect on the reaction rate.

Furthermore, the most important factors affecting β-hairpin stability were evaluated. Studies of tetrapeptide and decapeptide analogues revealed the essential role of the β-turn in initiation of hairpin folding. Moreover, hydrogen bonding was shown to be the main interchain stabilizing force, whereas hydrophobic interactions were found to be relatively weak. Nevertheless, hydrophobic packing appears to provide an important contribution to the thermodynamic stability of β-hairpins.

Photoswitchable peptidomimetics were prepared by incorporation of various stilbene moieties into tetra- and decapeptides. Synthesis, photochemical isomerisation and spectroscopic conformational analysis of the compounds were performed.

A microwave-enhanced, rapid, and efficient solidphase version of the Sonogashira reaction is presented. It has been applied to the coupling of aryl iodides and bromides with various acetylene derivatives giving excellent yields in 15 to 25 min. The scopes of homogeneous, solventless, and solid-phase conditions for Sonogashira coupling of aryl halides are compared.

This thesis describes free-radical reactions for the construction of tetrahydrofuran and pyrrolidine derivatives. The studies are concerned with (i) diastereoselectivity in radical cyclisation, (ii) construction of tetrahydrofuran-3-ones and pyrrolidin-3-ones via radical carbonylation/cyclisation and (iii) synthesis of tetrahydrofuran derivatives via group-transfer cyclisation of organochalcogen compounds.

(i) Diastereoselectivity in the synthesis of tetrahydrofuran derivatives via radical cyclisation was controlled by addition of Lewis acids. In the synthesis of 2,4-disubstitued tetrahydrofurans, the trans-isomer was formed as the major product in the unperturbed reaction. Upon addition of trialkylalumiums the diastereoselectivity was reversed. In a similar fashion, exo/endo-diastereoselectivity in the synthesis of bicyclic 2,3,4-trisubstituted tetrahydrofurans could also be controlled.

(ii) Procedures for construction of tetrahydrofuran-3-ones and pyrrolidin-3-ones were presented. Epoxides were ring-opened with benzeneselenolate or benzenetellurolate and the resulting β-hydroxyalkyl phenyl chalcogenides were vinylated using ethyl propiolate/NMM or E-1,2-bis(phenylsulfonyl)ethylene/NaH. The corresponding nitrogen analogues were accessed by N-vinylation of aziridines followed by benzeneselenolate ring-opening. The two types of organochalcogen radical precursors were then treated with TTMSS/AIBN under an atmosphere of carbon monoxide (80 atm) to afford tetrahydrofuran-3-ones and pyrrolidin-3-ones, respectively, in high yields.

(iii) Microwaves were found to induce group-transfer cyclisation of β-allyloxyalkyl aryl chalcogenides. Short time heating (3-10 min) at 250 ^oC in ethylene glycol was required to obtain tetrahydrofuran derivatives in 60-91% yield.

Compounds labelled with ¹¹C (β⁺, t_1/2 = 20.4 min) are used in positron emission tomography (PET), which is a quantitative non-invasive molecular imaging technique. It utilizes computerized reconstruction methods to produce time-resolved images of the radioactivity distribution in living subjects.

The feasibility of preparing [¹¹C]methyl iodide from [¹¹C]methane and iodine via a single pass through a non-thermal plasma reactor was explored. [¹¹C]Methyl iodide with a specific radioactivity of 412 ± 32 GBq/µmol was obtained in 13 ± 3% decay-corrected radiochemical yield within 6 min via catalytic hydrogenation of [¹¹C]carbon dioxide (24 GBq) and subsequent iodination, induced by electron impact.

Labelled ethyl-, propyl- and butyl iodide was synthesized, within 15 min, via palladium-mediated carbonylation using [¹¹C]carbon monoxide. The carbonylation products, labelled carboxylic acids, esters and aldehydes, were reduced to their corresponding alcohols and converted to alkyl iodides. [1-¹¹C]Ethyl iodide was obtained via palladium-mediated carbonylation of methyl iodide with a decay-corrected radiochemical yield of 55 ± 5%. [1-¹¹C]Propyl iodide and [1-¹¹C]butyl iodide were synthesized via the hydroformylation of ethene and propene with decay-corrected radiochemical yields of 58 ± 4% and 34 ± 2%, respectively. [1-¹¹C]Ethyl iodide was obtained with a specific radioactivity of 84 GBq/mmol from 10 GBq of [¹¹C]carbon monoxide. [1-¹¹C]Propyl iodide was synthesized with a specific radioactivity of 270 GBq/mmol from 12 GBq and [1-¹¹C]butyl iodide with 146 GBq/mmol from 8 GBq.

Palladium-mediated hydroxycarbonylation of acetylene was used in the synthesis of [1-¹¹C]acrylic acid. The labelled carboxylic acid was converted to its acid chloride and subsequently treated with amine to yield N-[carbonyl-¹¹C]benzylacrylamide. In an alternative method, [carbonyl-¹¹C]acrylamides were synthesized in decay-corrected radiochemical yields up to 81% via palladium-mediated carbonylative cross-coupling of vinyl halides and amines. Starting from 10 ± 0.5 GBq of [¹¹C]carbon monoxide, N-[carbonyl-¹¹C]benzylacrylamide was obtained in 4 min with a specific radioactivity of 330 ± 4 GBq/µmol.

This thesis describes the use of copper and palladium to mediate transformations of carboranes, especially p-carborane.

1-(1-p-carboranyl)-N-methyl-N-(2-butyl)-3-isoquinolinecarboxamide, a carborane containing analogue of the peripheral benzodiazepine receptor (PBR) ligand PK11195, has been synthesised. A key step in the reaction is the copper (I) mediated coupling of p-carborane with ethyl 1-bromo-isoquinoline-3-carboxylate.

p-Carborane has been arylated on the 2-B-atom in high yields, using the Suzuki–Miyaura reaction. Thus the reaction between 2-I-p-carborane and various arylboronic acids [1-naphthyl-, phenyl-, 4-MeO-C₆H₄-, 3-CH₃CONH-C₆H₄-, 4-NC-C₆H₄-, 3-NO₂-C₆H₄-], gave the corresponding 2-aryl-p-carboranes in DME solution when reacted in the presence of cesium fluoride and the catalytic Pd₂(dba)₃–dppb system. Under the same conditions, the boron-boron bond forming reaction of two p-carboranylboronic esters (2-[(pinacolato)boron]-p-carborane and 2-[(neopentyl glycolato)boron]-p-carborane) was also shown feasible.

p-Carborane has been vinylated on the 2-B-atom in high yields by use of the Heck reaction. The coupling between 2-I-p-carborane and various styrenes [4-H-, 4-C₆H₄-, 4-Cl , 4-Br-, 4-NO₂-, 4-CH3O- and 4 CH₃ ] resulted in the formation of the correspondingtrans-β-(2-B-p-carboranyl) styrene in DMF solution when reacted in the presence of silver phosphate and the palladacycle Herrmann´s catalyst. The reaction was shown to proceed at higher rate with electron rich than with electron deficient olefins.

The feasibility of palladium-catalysed isotopic exchange of an iodinated closo-carborane with a radioisotope of iodine has been studied. 2-I-p-carborane was selected as a model compound. It was shown, that such isotopic exchange is possible and provides a high yield (83 ± 4.2 %) during 40 min long reaction. The reaction conditions were optimised, and it was demonstrated that presence of the tetra n-butylammonium hydrogensulphate is important in order to stabilise catalyst and provide reproducibility of labelling. In this work we have modified the methodology and extended the application to a wider range of iodinated carboranes. By the use of Herrmann’s catalyst in toluene at 100 °C this [¹²⁵I]-iodide labelling could be improved and extended. 2-I-p- 9-I-m-, 9-I-o-, 3-I-o-carborane, 1-phenyl-3-I-o-carborane and 1,2-diphenyl-3-I-o-carborane could be [¹²⁵I]-iodide labelled in high to excellent yields within 5 minutes.This reported palladium catalyzed radio-iodination of the uncharged closo-carboranes might find use in pharmacokinetic studies of carborane derivatives.

Avenanthramides are amides of cinnamoyl-anthranilic acids and, among cereals, are exclusively found in oats. This study investigated the structure-antioxidant activities of 15 avenanthramides with different substitution patterns in the two aromatic rings, seven of which were new avenanthramides synthesised and characterised in this study. Radical-scavenging activity was tested as reactivity towards 1,1-diphenyl-2-picrylhydrazyl (DPPH-). The activity increased with the number of radical-stabilising groups ortho to the phenolic hydroxy group. Both aromatic rings were independently important for activity, while conjugation across the amide bond was of minor importance. Antioxidant activity was determined as inhibition of linoleic acid oxidation. In contrast to the radical-scavenging activity, antioxidant activity was observed for most avenanthramides, and also for compounds with only one hydroxy group in either of the aromatic rings. Compared with alpha-tocopherol, the avenanthramides protected linoleic acid from oxidation to a smaller extent initially, but the effect lasted for a longer time.

This thesis describes the synthesis and application of new chiral bicyclic ligands and their application in asymmetric catalysis. The studies involved: [i] The development of novel chiral bicyclic amino sulfur ligands and their use in transfer hydrogenation. [ii] The development of the kinetic resolution of racemic epoxide through the use of chiral lithium amides. [iii] The synthesis and application of chiral bicyclic amine in the organocatalysed epoxidation of alkenes. [iv] Development and application of new chiral diamine ligands in the rearrangement of epoxides into allylic alcohols.

[i] The preparation of two-series of amino thiol ligands based on the structure of camphor is described, together with their application in the iridium-catalysed asymmetric transfer hydrogenation of acetophenone using isopropanol as the hydrogen source. Excellent activity and good enantioselectivity have been achieved using 2 mol% of chiral ligand in combination with [IrCl(COD)]2.

[ii] The chiral diamines (1S,3R,4R)-3-(pyrrolidine-1-ylmethyl)-2-aza-bicyclo[2.2.1]heptane and its (2R,5R)-dimethylpyrrolidine derivative were applied to the kinetic resolution of a variety of racemic 5-7 membered cycloalkene oxides with lithium diisopropylamide (LDA) as the bulk base. Using 5 mol% of the chiral diamines, both unreacted epoxides and allylic alcohols could be produced in enantiomeric excess up to 99%.

[iii] The synthesis of chiral bicyclic amines and their use in the organocatalysed epoxidation of alkene has been described. Using a substoichiometric amount of the chiral amines and aldehydes as ligands precursors, with Oxone® as oxidant, a good activity but moderate enantioselectivity was observed for the epoxidation of trans-stilbene.

[iv] The preparation of 6-substituted-7-bromo-aza-bicyclo[2.2.1]heptanes via nucleophilic addition of organocopper reagents to 3-bromo-1-azoniatricyclo[2.2.1.0]heptyle bromide has been described. These compounds have been utilised as chiral building blocks in the preparation of novel chiral diamine ligands, which have been successfully applied to the catalysed asymmetric rearrangement of epoxide into the corresponding allylic alcohol.

We describe herein an efficient method for the preparation of a functionalised bicyclic framework (6-substituted 7-bromo-aza-bicyclo[2.2.1]heptane) through the selective opening of the aziridium 2 with organocuprates in up to 90% yield. These interesting chiral building blocks were then utilised as novel ligands in the rearrangement of epoxides to afford chiral allylic alcohols.

This thesis describes synthesis and reactivity studies of 2-amino-2-siloxysilenes and 2-silenolates, species that are strongly influenced by reversed Si=C bond polarization, i.e. an Si^δ-=C^δ+ polarization as compared to the natural Si^δ+=C^δ- polarization. Because of the reversed polarization, the 2-amino-2-siloxysilenes are zwitterions and the 2-silenolates are predominantly described by the resonance structure with the negative charge at Si.

Transient zwitterionic 2-amino-2-siloxysilenes are formed thermolytically from carbamylpolysilanes (tris(trimethylsilyl)silylamides) and trapped with 1,3-dienes in nearly quantitative yields. These silenes have structure and reactivity characteristics that differ from earlier studied Si=C bonded compounds. They are thermodynamically stable toward dimerization and react with 1,3-dienes to give exclusively [4+2] cycloadducts. Their reactions with 1,3-dienes proceed in accordance with inverse electron demand (IED) Diels-Alder reactions which is explained by the electron-rich nature of these silenes. The 2-amino-2-siloxysilenes are also less reactive toward alcohols than earlier silenes. Hence, alcohols do not react with 2-amino-2-siloxysilenes but with the silene precursor, the carbamylpolysilanes, leading to alkoxysilanes in high yields. The latter reaction represents a novel base-free synthetic protocol for protection of primary and secondary alcohols with the fluoride resistant but photolabile tris(trimethylsilyl)silyl group.

Another class of formally Si=C bonded compounds, metal 2-silenolates, has been formed in high yields using a novel facile method. Reaction of acyl- and carbamylpolysilanes with potassium tert-butoxide in tetrahydrofurane gives potassium 2-silenolates. The potassium 2-silenolates are stable at room temperature, in contrast to earlier lithium 2-silenolates that degrade rapidly at ambient temperature. The first crystallisable complex of a 2-silenolate was formed and characterized by X-ray crystallography. This 2-silenolate has a pyramidal central Si (ΣSi = 317.8°), and an Si-C single rather than Si=C double bond (r(SiC) = 1.926 Å). The potassium 2-silenolates give exclusively Si alkylated products with alkyl halides and only [4+2] cycloadducts with 1,3-dienes.

The enzymatic kinetic resolution of 1-(3-furyl)-3-buten-1-ol was investigated via the enantioselective hydrolysis of the corresponding acetate. Pseudomonas fluorescens (Fluka) was found to give the highest enantiomeric ratios of the 11 lipases screened. At 51% conversion, the ee value (ee_p) for the product was found to be 89%, giving an enantiomeric ratio (E_p) of 58, while the ee value (ee_s) for the substrate was 89%, giving an enantiomeric ratio (E_p) of 38.

Breast cancer is the most frequent invasive malignancy and the second major cause of cancer death in female subjects mostly due to the considerable diagnostic delay and failure of therapeutic strategies. Thus, early diagnosis and possibility to monitor response to the treatment are of utmost importance. Identification of valid biomarkers, in particular new molecular therapeutic targets, that would allow screening, early patient identification, prediction of disease aggressiveness, and monitoring response to the therapeutic regimen has been in the focus of breast cancer research during recent decades. One of the intensively developing fields is nuclear medicine combining molecular diagnostic imaging and subsequent (radio)therapy in the light of theranostics. This review aimed to survey the current status of preclinical and clinical research using theranostic approach in breast cancer patients with potential to translate into conventional treatment strategies alone or in combination with other common treatments, especially in aggressive and resistant types of breast cancer. In addition, we present 5 patients with breast cancer who were refractory or relapsed after conventional therapy while presumably responded to the molecular radiotherapy with Lu-177-trastuzumab (Herceptin), Lu-177-DOTATATE, and Lu-177-FAPI-46.

[¹¹C]Carbon monoxide in low concentrations has been used in palladium- or seleniummediated carbonylation reactions such as the synthesis of ¹¹C-imides, hydrazides, amides, carboxylic acids, esters, carbothioates, ketones and carbamoyl compounds.

In these reactions aryl iodides have been used in most cases. However, less reactive aryl triflate, chloride and bromides were activated using tetrabutylammonium iodide.

The reactivities of nucleophiles may have influence on the radiochemical yield of the ¹¹Clabelled compounds. Carboxyamination of aryl halides using aniline derivatives yielded 10% of the corresponding ¹¹C-amide. However, the radiochemical yields increased significantly when the aniline derivatives were treated with lithium bis(trimethylsilyl)amide. In contrast, this reagent did not improve the radiochemical yields when primary amines such as methylamine and benzylamine were used. In these cases the radiochemical yields were improved by using pempidine.

¹¹C-Esterification usually gave low yields. However, the radiochemical yields of ¹¹C-esters could be improved by using magnesium bromide and pempidine.

An excess of ligand may have a significant impact on palladium-promoted carbonylation reaction. The radiochemical yields of ¹¹C-ketones were improved when using excess amounts of tri-o-tolylphosphine.

(¹³C)Carbon monoxide may be utilized for the synthesis of ¹³C-substituated compounds in order to confirm the position of ¹¹C-labelling.

We propose radionuclide imaging as a valuable tool for the study of molecular interactions in miniaturized systems for chemical analysis. Sensitive and quantitative imaging can be performed with compounds labeled with short-lived positron-emitting radionuclides, such as C-11 and Ga-68, within selected parts of the system. Radionuclide imaging is not restricted to transparent materials since the relatively energetic positrons can penetrate high optical density materials. Experimentally, a radiotracer is introduced into the object of study, which is subsequently placed on a phosphor storage plate. After exposure, the plate is scanned with a laser and a digital, quantitative image can be reconstituted. To demonstrate the concept, three types of microstructures suited for integration in chemical analysis systems were imaged with C-11- and Ga-68-labeled tracers. The influence of factors such as geometry of the object and type of radionuclide on resolution and sensitivity was investigated. The resolution ranged from 0.9 to 2.7 mm (fwhm). Measuring low amounts of radioactivity in the three structures, 2-20 Bq could be detected, which corresponded to 2.3-500 amol or 2.4-110 pM tracer. The imaging approach was applied to study analyte concentration and sample dilution effects on the performance of a capillary extraction column integrated in an automated LC-ESI-MS system. The utility of the technique was further illustrated by imaging of microchannels in a zeonor plastic compact disk and in a poly(dimethylsiloxane) material for the study of nonspecific peptide adsorption.

Five N-substituted derivatives of 1,2-methylene-3,4-aziridino 2-phenylsulfonyl cycloalkanes (3a-e) were prepared from their corresponding epoxy cyclopropanes via ring opening of the epoxide by sodium azide and subsequent triphenylphosphine induced cyclization. BF₃-induced reaction of compounds 3a-e resulted in a rearrangement via a cyclopropyl carbinyl cation intermediate. In the case of tosylaziridine 3c bicyclic product 5, (tropane skeleton), was formed as the major product. With carbamate derivative 3a exclusive rearrangement to fluorocyloheptene 7 took place.

Solvolysis of the R,R and R,S isomers 2a-X and 2b-X, respectively, (X = I, Br, OBs) in 25 vol % acetonitrile in water gives the elimination products 4, 5a, and 5b along with the substitution products 2a-OH, 2b-OH, 2a-NHCOMe, and 2b-NHCOMe. The rates of e

This thesis describes the development and evaluation of new chiral Ru(arene)(amino alcohol) catalysts for the transfer hydrogenation of aromatic ketones using isopropanol as the hydrogen source. Two mechanistic studies of the Ru(arene)(amino alcohol) catalyzed transfer hydrogenation of acetophenone were also conducted.

The Ru(arene)[(1S,3R,4R)-3.(Hydroxymethyl)-2-azabicyclo[2.2.1]heptane] catalyst was optimized for catalytic asymmetric transfer hydrogenation of aromatic ketones. The effect of substituents on the arene ligand on both selectivity and reactivity was investigated. The performance of the catalyst was also optimized by altering the structure of the chiral amino alcohol ligand. These optimizations resulted in a highly active and selective catalyst, Ru(p-cymene)[(R)-1-[(1S,2R,6S,7R,9R)-4,4-Dimethyl-3,5-dioxa-8-aza-tricyclo[5.2.1.0^0,0]dec-9-yl]-ethanol], for asymmetric transfer hydrogenation of aromatic ketones. This catalyst was capable of reducing acetophenone in 96% ee in 4 minutes at room temperature at a substrate to catalyst ratio of 200. Full conversion was reached even at a substrate to catalyst ratio of 5000 and the high enantioselectivity of 96% ee was maintained. A range of prochiral aromatic ketones with electron withdrawing or electron donating substituents in any position on the aromatic ring were reduced in short reaction times and with high enantioselectivity, up to 99% ee. Bulky aryl alkyl ketones were also reduced with high enantioselectivity.

A combined quantum chemical and kinetic investigation of the Ru(arene)(amino alcohol) catalyzed transfer hydrogenation of acetophenone was conducted. Three possible mechanisms were studied and the quantum chemical calculations indicated that the mechanism was concerted. In addition, a kinetic isotope study for the Ru(arene)(amino alcohol) catalyzed transfer hydrogenation of acetophenone was conducted. The determination of the kinetic isotope effect of the proton and hydride transfer showed that the proton and the hydride transfer were both rate-limiting and occurred in the same step. This result supports the proposed concerted mechanism.

The beauty of the wide functionality of proteins and peptides in Nature is determined by their ability to adopt three-dimensional structures. This thesis describes artificial molecules developed to mimic secondary structures similar to those found crucial for biological activities.

In the first part of this thesis, we focused on post-translational modifications of a class of unnatural oligomers known as β-peptides. Through the design and synthesis of a glycosylated β³-peptide, the first such hybrid conjugate was reported. In this first report, a rather unstable 3₁₄-helical structure was found. Subsequently, a collection of six new glycosylated β³-peptides was synthesized with the aim to optimize the helical stability in water.

The ability of natural proteins, i.e. lectins, to recognize the carbohydrate residue on these unnatural peptide backbones was investigated through a biomolecular recognition study.

The second part of this thesis concerns the design of conformationally homogeneous scaffolds, which could be of importance for biomedical applications. In paper V, four- and five-membered cyclic all-β³-peptides were investigated for this purpose. In a subsequent paper, a completely different strategy was employed; herein, the ability of a single β²-amino acid to restrict the conformational freedom of a cyclic α-peptide was studied.

In the third part of this thesis, we synthesized and investigated the folding propensities of novel backbone modified oligomers, i.e. β-peptoids (N-substituted β-Ala) with α-chiral side chains.

The collective results of these studies have established the procedures required for synthesis of glycosylated β-peptides and deepened our understanding of the factors governing folding among such oligomers. Moreover, it was established that β-amino acids can be a useful tool to increase conformational stability of cyclic peptides.