Among Nature’s creation, terpenoids are more versatile and exciting natural products. In a remarkable display of synthetic ingenuity and creativity, nature has endowed terpenes with a bewildering array of carbocyclic frameworks with unusual assemblage of rings and functionalities. This phenomenal structural diversity of terpenes make them ideal targets for developing and testing new synthetic strategies for efficient articulation of carbocyclic frameworks. The thesis entitled “Total synthesis of sesquiterpenes acorenols, chamigrenes, and laurokamurene B; and Enantiospecific synthesis of ABC-ring system of A-nor and abeo pentacyclic triterpenes” describes the studies directed towards the total synthesis of the sesquiterpenes mentioned in the title and exploratory studies towards triterpenoids. In each chapter of the thesis, the compounds are sequentially numbered (bold) and references are marked sequentially as superscripts and listed at the end of the chapter. All the spectra included in the thesis were obtained by xeroxing the original NMR spectra. The sesquiterpenes acorenols, containing an interesting spiro[4.5]decane carbon framework, was first isolated in 1970 by the research group of Tomita from the wood of Juniperus rigida. Recently, in 2003, Braun and coworkers reported the isolation of epi α- and epi β-acorenols along with α- and β-acorenols from the sandal wood oil Santalum spicatum. Total synthesis of all the four acorenols has been described in the first part of the first chapter of the thesis. Initially, a model study has been carried out for the spirocyclopentannulation of cyclohexanone employing a combination of Ireland ester Claisen rearrangement and ring closing metathesis reaction to furnish methyl 4-methylspiro[4.5]dec-3-en-1-carboxylate. The same methodology has been extended for the total synthesis of all the four acorenols starting from cyclohexane-1,4-dione via cis and trans isomers of methyl 4-methyl-8-methylene-spiro[4.5]dec-3-ene-1-carboxylate. Total synthesis of β-chamigrene, γ-chamigrene and laurencenone C, containing spiro[5.5]undecane carbon framework, has been described in the second part of the first chapter. As a model study, cyclohexanone has been transformed into 1,5,5-trimethylspiro-[5.5]undec-4-en-3-one employing a combination of Ireland ester Claisen rearrangement and intramolecular type-II carbonyl ene reactions. The methodology has been extended to chamigrenes starting from cyclohexane-1,4-dione via methyl 2-(1-isopropenyl-4-oxocyclo-hexyl)-2-methylpropanoate and 5,5-dimethyl-1,9-ismethylenespiro[5.5]undecan-3-ol. The marine sesquiterpenes laurokamurenes were first isolated in 2006 by Mao and Guo from Laurencia okamurai Yamada. First total synthesis of (±)-laurokamurene B has been described in the first part of the second chapter. To begin with Ireland ester Claisen rearrangement of but-2-enyl 2-methylpropionate furnished methyl 2,2,3-trimethylpent-4-enoate, which was then transformed into 4,5,5-trimethyl-3-(4-methylphenyl)hepta-1,6-dien-3-ol. RCM reaction followed by reductive deoxygeneation transformed 4,5,5-trimethyl-3-(4-methylphenyl)hepta-1,6-dien-3-ol into (±)-laurokamurene B. Subsequently, an enantioselective total synthesis of (+)-laurokamurene B has been accomplished. Stereoselective hydrogenation of methyl campholenoate furnished methyl 2-[(1S,3S)-2,2,3-trimethyl-cyclopent-1-yl]acetate, which was then transformed into (+)-laurokamurene B via degradation of the two carbon side chain and introduction of the aryl moiety, which established the absolute configuration of laurokamurenes. The third chapter deals with the enantiospecific generation of ABC-ring system of A-nor and abeo 4(3 → 2) tetra and pentacyclic triterpenes. To begin with (R)-carvone was identified as B-ring of ABC-ring system of A-nor and abeo tetra and pentacyclic triterpenes, as the absolute configuration at the C-5 position of the targets correlate to the stereo centre of carvone, and isopropenyl group can serve as the C-4 carbon of the targets along with the two gem-dimethyl groups. A lithium liquid ammonia mediated cyclisation of δ,ε-unsaturated esters was employed for the construction of the A ring and an RCM reaction was opted for the construction of the C ring. (R)-Carvone has been converted into 2-(1-ethoxyethoxy)-1,3,7,7-tetramethylbicyclo[4.3.0]non-3-en-8-ol via lithium liquid ammonia mediated cyclisation of methyl 2-(1-ethoxyethoxy)-6-isopropenyl-1,3-dimethylcyclohex-3-enyl]acetate, which was then transformed into 4-methoxymethoxy-2,5,5,9-tetramethyltricyclo[7.4.0.02,6]tridec-11-en-8-one via the RCM reaction of 3,4-bisallyl-8-methoxymethoxy-4,6,9,9-tetramethylbicyclo-[4.3.0]nonan-3-one. The strategy has been further extended to the synthesis of 4-methylene-2,5,5,9-tetramethyltricyclo[7.4.0.02,6]tridec-11-en-8-one, which contains the ABC ring system of abeo 4(3→2) tetra and pentacyclic triterpenes.

I den här avhandlingen har vi studerat hur man kan göra nya tensider. En tensid är en speciell molekyl som har förmågan att lösa sig i både vatten och olja. Man kan göra följande experiment hemma: Fyll en glasburk till hälften med vatten och tillsätt en droppe matolja. Oljan bildar en droppe ovanpå vattnet, därför att vatten och olja inte är blandbara. Vatten är polärt och olja är opolärt. Om man rör om med en sked kommer oljedroppen förvisso att dela upp sig i mindre droppar, men så snart man slutar att röra kommer dessa att lägga sig på vattenytan igen. Sätt nu en droppe diskmedel till blandningen och rör om. Nu sprider sig oljedropparna mycket bättre i vattnet, och de lägger sig heller inte på vattenytan lika fort när man slutar att röra. Det här beror på att diskmedel innehåller en tensid, som har en polär och en opolär del. Den polära delen passar ihop med det polära vattnet, medan den opolära delen passar ihop med den opolära oljan. På så vis kan tensiden hjälpa till att lösa upp opolära ämnen i polära vätskor. Den aktiva delen av ett läkemedel består ofta av opolära ämnen, vilka inte löser sig i polära vätskor såsom vatten. Eftersom kroppen består till stor del av vatten måste man ändå försöka få läkemedlet vattenlösligt, för att möjliggöra transport via blodet till problemområdet. Det kan man uppnå genom att tillsätta tensider. Om läkemedel-tensidblandningen ska ges till djur eller människor får inte tensiden orsaka någon skada i kroppen. Vi har försökt framställa tensider som ska kunna användas för att just lösa läkemedel i vatten. För att kunna framställa nya tensider måste man ha kunskap i organisk syntes. Det betyder att man måste veta hur man från små intermediat (”byggstenar”) successivt kan bygga upp nya molekyler som har de önskvärda egenskaperna. Genom olika typer av organisk syntes har vi byggt upp tre nya tensidtyper, vars egenskaper vi studerat med olika mätningar. Ingen av dessa tensider lämpade sig som tillsats till läkemedel, men vårt arbete har givit mycket ny kunskap om hur framtida tensidmolkyler kan tillverkas och vilka egenskaper de får. / This thesis deals with the synthesis and characterization of new polyhydroxy surfactants. The first part describes the synthesis of three new surfactant classes, and the second part concerns the surface chemical characterization of the synthesized surfactants. A stereodivergent route for preparation of hydrophilic head groups was developed, that featured consecutive stereoselective dihydroxylations of a diene. This method provided in total four different polyhydroxylated head groups. These surfactant head groups were natural and unnatural sugar analogues, and were used for the coupling with two different hydrophobic tail groups. Another approach took advantage of a metathesis reaction and provided a polyhydroxylated compound that was coupled to 12-hydroxy stearic acid The third class of surfactants contained an amide linkage between the hydrophilic and the hydrophobic parts. The hydrophilic part consisted of two glucose units, and 12-hydroxy stearic acid was used as the hydrophobic part. The hydroxy moiety in the tail group was further functionalized as aliphatic esters, which provided in total four different surfactants. A selection of the surfactants was used to investigate the chiral discrimination in Langmuir monolayers at an air-water interface. The isotherms showed a remarkable difference in compressibility between diastereomeric surfactants and also a pronounced chiral discrimination between racemic and enantiomerically pure surfactants, favoring heterochiral discrimination. The monolayers were also investigated with Brewster angle microscopy (BAM) and grazing incidence X-ray diffraction (GIXD). It was not possible to observe any chirality dependent features from the BAM images, but the GIXD measurement supported the conclusion that heterochiral discrimination governed the intermolecular forces within the racemic monolayer. The third class of surfactants, containing an amide linkage between the glucose units and 12-hydroxy stearic acid was evaluated with respect to the CMC and the haemolytic activity. These surfactants were all haemolytic close to their respective CMC. / QC 20101015

A major driving force for development of new catalyst systems is the need for more efficient synthesis of chemical compounds essential to modern life. Catalysts having superior performance offer significant environmental and economic advantages, but their discovery is not trivial. Well-defined, homogeneous catalysts can offer unparalleled understanding of ligand effects, which proves invaluable in directing redesign strategies. This thesis work focuses on the design of ruthenium complexes for applications in dinitrogen activation and olefin metathesis. The complexes developed create new directions in small-molecule activation and asymmetric catalysis by late-metal complexes. Also examined are the dual challenges, ubiquitous in catalysis, of adequate interrogation of catalyst structure and performance. Insight into both is essential to enable correlation of ligand properties with catalyst activity and/or selectivity. Improved methods for accelerated assessment of catalyst performance are described, which expand high-throughput catalyst screening to encompass parallel acquisition of kinetic data. A final aspect focuses on direct examination of metal complexes, both as isolated species, and under catalytic conditions. Applications of charge-transfer MALDI mass spectrometry to structural elucidation in organometallic chemistry is described, and the technique is employed to gain insight into catalyst decomposition pathways under operating conditions.

The use of polymer supports for transition metal catalysts are very important and useful in synthetic organic chemistry as they make possible the separation and isolation of catalysts and products quite easy. These polymer-bound ligands/catalysts/reagents can, often, be recovered and recycled numerous times and typically yield products in high purity, negating the need for further purification steps (i.e. column chromatography). Because of this, interest in these systems has garnered international attention in the scientific community as being “Green”. Historically, insoluble, polymer-supports (i.e. Merrifield resin) were used to develop recoverable catalysts. This has the advantage of easy separation and isolation from products after a reaction; because of their insolubility, such supported catalysts can be easily removed by gravity filtration. However, these catalysts often have relatively poor reactivity and selectivity when compared to homogeneous catalysts. Because of this disadvantage, our lab has had interest in the development of soluble polymer-supports for transition metal catalysts. We have developed several separation methods for these soluble polymer-bound catalysts. These include thermomorphic liquid/liquid and solid/liquid as well as latent biphasic liquid/liquid separation techniques. This dissertation describes the use of both, latent biphasic liquid/liquid separation systems and thermomorphic solid/liquid separation systems. In order to perform a latent biphasic iii liquid/liquid separation, a polymer-bound catalyst must have a very high selectivity for one liquid phase over the other. Our lab has pioneered the use of polyisobutylene (PIB) oligomers as supports for transition metal catalysts. Previous work has shown that these oligomers are > 99.96 % phase selectively soluble in nonpolar solvents. This has allowed us to prepare PIB-supported salen Cr(III) complexes that can be used in a latent biphasic liquid/liquid solvent system. The synthesis of these complexes is quite straightforward and such species can be characterized using solution state 1H and 13C NMR spectroscopy. Also, these complexes can be used to catalyze the ring opening of meso epoxides with azidotrimethylsilane (TMS-N3) and can be recovered and recycled up to 6 times, with no loss in catalytic activity. To perform a thermomorphic solid/liquid separation, a polymer-bound catalyst that is completely insoluble at room temperature but soluble upon heating must be used. Our lab has pioneered the use of polyethylene oligomers (PEOlig) as supports for transition metal catalysts. Such PEOlig-supported catalysts are able perform homogeneous catalytic reactions at elevated temperatures (ca. 65 ○C), but, upon cooling, precipitate out of solution as solids while the products stay in solution. This process allows for the easy separation of a solid catalyst from the product solution. Described herein, is the development of PEOlig-supported salen-Cr(III) complexes and PEOlig-supported NHC-Ru complexes. The preparation of these complexes is also straightforward and such species can be characterized using solution state variable temperature (VT) 1H and 13C NMR spectroscopy. In the case of the PEOlig-supported salen-Cr(III) complex, it was found to be a recoverable/recyclable catalyst for the ring opening of epoxides with TMS-N3 and could be reused 6 times with no loss in activity. The PE-supported NHC-Ru complex was able to be used as a recyclable ring closing metathesis (RCM) catalyst and could be used up to 10 times.

A major driving force for development of new catalyst systems is the need for more efficient synthesis of chemical compounds essential to modern life. Catalysts having superior performance offer significant environmental and economic advantages, but their discovery is not trivial. Well-defined, homogeneous catalysts can offer unparalleled understanding of ligand effects, which proves invaluable in directing redesign strategies. This thesis work focuses on the design of ruthenium complexes for applications in dinitrogen activation and olefin metathesis. The complexes developed create new directions in small-molecule activation and asymmetric catalysis by late-metal complexes. Also examined are the dual challenges, ubiquitous in catalysis, of adequate interrogation of catalyst structure and performance. Insight into both is essential to enable correlation of ligand properties with catalyst activity and/or selectivity. Improved methods for accelerated assessment of catalyst performance are described, which expand high-throughput catalyst screening to encompass parallel acquisition of kinetic data. A final aspect focuses on direct examination of metal complexes, both as isolated species, and under catalytic conditions. Applications of charge-transfer MALDI mass spectrometry to structural elucidation in organometallic chemistry is described, and the technique is employed to gain insight into catalyst decomposition pathways under operating conditions.

This dissertation describes the synthesis of molecular machines designed to operate on surfaces (nanocars) or in the solution phase (nanosubmarines), and the study of their diffusion using fluorescence techniques. The design of these molecular machines is aimed to facilitate monitoring of their movement and incorporation of a source of energy for propulsion. To complement previous scanning tunneling microscopy studies of the translation of nanocars on surfaces, chapter 1 describes the synthesis of a family of fluorescently tagged nanocars. The nanocars were functionalized with a tetramethylrhodamine isothiocyanate (TRITC) fluorescent dye. Single-molecule fluorescence microscopy (SMFM) studies of one of these nanocars revealed that 25% of the nanocars moved on glass. The SMFM results also suggested that the dye hindered the mobility of the nanocars. Seeking to improve the mobility, chapter 2 presents the synthesis of a new set of fluorescent nanocars, featuring a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dye embedded in their axles. The mobility of these inherently fluorescent nanocars on glass was nearly double than that of their TRITC-tagged predecessors. Their diffusion was also studied on reactive-ion-etched glass, and amino-functionalized glass. The results showed that the mobility is affected by the substrate. To equip the nanocars with an energy input for propulsion, two nanocars functionalized with an olefin metathesis catalyst were synthesized, as described in chapter 3. The catalytic activity of these nanocars toward ring-opening metathesis polymerization (ROMP) in solution was similar to that of their parent catalysts. As an alternative approach to investigate if chemical propulsion through a ROMP process can be achieved at the molecular level, chapter 4 presents the synthesis of a fluorescent ROMP catalyst, termed a nanosubmarine, and the study of its diffusion using fluorescence correlation spectroscopy (FCS). FCS results showed an increase of 20 ± 7% in the diffusion constant of this nanosubmarine in presence of its fuel, cis,cis-1,5-cyclooctadiene. Overall, the work accomplished in this dissertation constitutes a step forward toward development of easily tracked and highly mobile nanocars, and paves the way for the synthesis of truly nanosized chemically propelled molecular machines that operate in the solution phase.

Reaction of 3-sulfonyl acetamides with various substituted methyl acrylate derivatives furnished pyroglutamate and glutarimidess via [3+2] and [3+3] cycloaddition respectively. The results were applied to the synthesis of pyrrolizidine skeleton, tylophorine, cryptopleurine and fused bicyclic glutarimides.

Chapter 1: Reaction of benzoaldehyde with wittig agents or isophone to build up conjugate carbon chain, then combined with electron acceptor to furnished the chromophores. The charge-transfer chromophores, which have the first molecular hyperpolarizability

We use stepwise [3+3] annulation to prepare the asymmetric glutarimides, and then establish a new approach to isoquinolone skeleton starting from glutarimides via regioselective nucleophilic addition and ring-closing metathesis reaction. Finally, we applied this method to the synthetic studies toward (¡Ó)-Xylopinine.

The thesis subject is mainly involved in Green Chemistry approach. Thiophene, furan and pyridine carboxaldehydes were chosen as starting compounds and vinylation and allylation with Grignard reaction afforded the corresponding racemic heteroaryl substituted allylic and homoallylic alcohols. Subsequent resolution with enzymes (PS-Amano II, Lipozym and Novazym 435) gave enantiomerically enriched alcohols with the e.e. values varied between 65 and 99%. The absolute configurations of all substrates are known. As a result of O-allylation with the common procedure formed the feasible carbon backbone for the ring closing metathesis reaction. All ring closing metathesis reactions were performed by Grubbs&rsquo / catalyst with just 5% catalyst loading. The absolute configurations of dihydrofuran and dihydropyran derivatives are known, since the chiral center configurations of all substrates are preserved throughout all the applied processes.