The thesis entitled ‘Chemistry of molybdenum xanthate (MoO2[Et2NCS2]2): Applications in organic synthesis’ is presented in 4 chapters. Molybdenum (IV and VI) oxo-complexes are the subject of significant interest due to their functional and structural similarities with several molybdo-enzymes.1 Literature survey suggests that, molybdenum (VI as well as IV) xanthate2 1 resembles the active sites of various molybdo-enzymes. Therefore, in the present thesis, we are presenting our attempts directed towards exploiting molybdenum xanthate 1 in developing various useful methodologies. Figure 1: Molybdenum xanthate Chapter 1 discloses the utility of molybdenum xanthate (1) in catalytic, aerobic oxidation of organic azides and alcohols as presented in part A and B. Part A: A mild molybdenum xanthate catalyzed, chemoselective oxidation of benzylic azides to the corresponding aldehydes3 under aerobic condition is described. This oxidation turned out to be a general method and a variety of benzylic azides were oxidized to the corresponding aldehydes. This oxidation protocol tolerates a variety of functional groups including alcohols, esters, ketones, halides and olefins. More importantly, the oxidation of azides stops at corresponding aldehyde stage without further oxidation to the corresponding carboxylic acids. A few examples are presented in scheme 1. Part B: As our attempts to oxidize alcohols with molybdenum xanthate 1 were unsuccessful (Chapter 1, Part A), we have attempted supporting the reagent 1 and investigated its utility in the oxidation of alcohols. As a consequence, polyaniline supported molybdenum xanthate (MoO2[Et2NCS2]2) is designed and used in an aerobic and mild chemoselective oxidation of alcohols4 to the corresponding aldehydes and ketones. The scheme to use polyaniline as the support for molybdenum xanthate was derived from the fact that polyaniline is known to increase the redox activity of various metal complexes by coordinating to the metal centre.5 The present oxidation strategy tolerates a variety of functional groups such as olefin, ketones, sulfides, tertiary amines, propargyl group etc. This oxidation strategy also works very well for the oxidation of secondary benzylic alcohols. Interestingly, the supported catalyst can be filtered after the reaction and reused for further oxidation without loss of its activity. Some representative examples are presented in Scheme 2. Chapter 2 describes the chemoselective and efficient reduction of azides to the corresponding amines. In this chapter, we have shown that a catalytic amount of molybdenum xanthate (1, MoO2[S2CNEt2]2) with PhSiH3 is an effective catalyst for the reduction of azides to the corresponding amines.6 This reduction of azides by 1, was inspired by the reductive silylation of aldehydes through the activation of silanes.7 This reduction tolerates a variety of reducible functional groups such as olefin, aldehydes, ketones, esters, amides and ethers, acetals etc. This strategy was also extended to various aliphatic azides to synthesize amine and their N-Boc derivatives in good yields. Scheme 3 illustrates few examples. Chapter 3 discloses convenient methods for the synthesis of substituted thiourea derivatives as presented in part A and B. Part A: A convenient method for the synthesis of tri-substituted thiourea derivatives by the reaction of primary amines with molybdenum dialkyl dithiocarbamates is presented in Part A.8 Primary amines on reaction with molybdenum xanthate produce corresponding thioureas in moderate to good yields. Similar reactions with propargylamine and 2-aminoethanol produce cyclic thiaoxazolidine and oxazolidine derivatives respectively. This methodology has been successfully adopted for the synthesis of amino acids derived chiral thioureas. Some examples are presented in Scheme 4. Scheme 4: Molybdenum xanthate mediated synthesis of thioureas Part B: An efficient method for the synthesis of symmetrical and unsymmetrical substituted thiourea9 derivatives by simple condensation of amine and carbon disulfide in aqueous medium is extensively studied. Present method describes the involvement of amino dithiol moiety as an intermediate. Though this method is not successful with secondary amines and aryl amines, it works smoothly with aliphatic primary amines to afford various di- and tri-substituted thiourea derivatives. The present method is also useful in synthesizing various substituted 2-mercapto imidazole heterocycles in moderate yields. A few examples are seen in Scheme 5. Scheme 5: Synthesis of thiourea derivatives in aqueous medium Chapter 4 describes a chemoselective deprotection10 of terminal acetonides (isopropylidines) by using aqueous TBHP (70%). A variety of acetonide derivatives on reaction with aq. TBHP in water:t-BuOH (1:1) as solvent mixtures furnish the corresponding acetonide deprotected diol products in good yields. This unprecedented deprotection strategy, tolerates a variety of acid sensitive functional groups such as silyl ether, trityl, olefin, propargyl, methoxymethyl ether, N-Boc, lactones, esters etc. A few examples are documented in Scheme 6. Scheme 6: Chemoselective deprotection of acetonides (For structural formula pl see the pdf file)

Cyclopropanes are strained molecules and undergo reactions, for example, through ring opening and rearrangements. Preparative methods and reactivities of cyclopropanes are known widely in organic synthesis. The high reactivities inherent in cyclopropanes allow them to be valuable building blocks in organic synthesis. The combination of cyclopropanes and carbohydrates has been explored in recent years. Carbohydrates, the naturally-occurring members of chiral pool, are attractive platforms for asymmetric synthesis. Cyclopropanation of, for example, unsaturated sugars affords [4.1.0] bicyclic systems, thereby combining the high reactivities of cyclopropanes together with optical purities of sugars. Chapter 1 of the Thesis describes (i) various types of cyclopropane ring opening reactions in general and (ii) known reactions of cyclopropanes in carbohydrates relevant to the work presented in the Thesis. Seven-membered cyclic sugars, namely, septanoses and septanosides, are less commonly known sugar homologues. Synthesis of septanoses arise interest, due to their configurational and conformational features and the attendant possibilities to explore their chemical, physical and biological properties. In a programme, it was desired to identify a new methodology for synthesis of septanosides. It was envisaged that 2-hydroxy glycals, namely, oxyglycals, would form as suitable substrates for ring expansion, leading to the formation of septanoside derivatives that are retained with hydroxyl groups in each carbon of the septanoside. In the event, a new methodology was identified. A carbene insertion of an oxyglycal substrate, nucleophilic ring opening of the cyclopropyl moiety, oxidation and reduction reactions were identified to expand the six membered pyranoses to seven membered septanosides (Scheme 1). The methodology was established through preparation of two configurationally different septanosides, namely, the methyl α-D-glycero-D-talo-septanoside and methyl α-D-glycero-L-altro-septanoside from D-glucose and D-galactose, respectively. Chapter 2 presents details of the methodology and the preparation of septanosides from precursors oxyglucal and oxygalactal. Scheme 1 Continuing the efforts to extend the methodology, preparation of a variety of septanosides, using phenoxides, sugars and azide were undertaken. It was found that ring opening with sugars were highly stereoselective, leading to an exclusive formation of the -anomer of sugar oxepines, whereas, the phenoxides and azide led to a mixture of anomers of the corresponding oxepines, in a ~1:1 ratio (Scheme 2). Scheme 2 An important observation was -anomer of the oxepine derived intermediates, having diketo-functionalities, underwent NaBH4 mediated conversion to diols with higher diastereoselectivities at the newly generated stereo-centers, whereas the -anomers lacked to retain the diastereoselectivities, in the case of aryl septanosides. This part of work consolidated further the generality of the oxyglycal ring-expansion method to prepare septanosides, possessing different substituents at their reducing ends. Chapter 3 describes the details of syntheses and characterization of various aryl septanosides, septanoside disaccharides and azido-septanoside derivatives. It was planned further to synthesize septanoside containing di-and trisaccharides from naturally-occurring disaccharides, through the oxyglycal route. Oxyglycals, derived from lactose and maltose, were expanded to septanoside-containing trisaccharides through a ring expansion method. Thus septanosides incorporated disaccharides and trisaccharides, with 6-7, 6-7-5 and 6-7-6 ring sizes, were prepared through the ring expansion method. The reaction not only led to a ring expansion, but also, to a concomitant glycoside formation, in a stereoselective manner (Scheme 3). Scheme 3 A conformational analysis of the galacto-septano-glucopyrano-configured 6-7-6 trisaccharide was undertaken with aid of NMR spectroscopy and computational methods. Spatial distances from NMR experiments were utilized while performing molecular dynamics with AMBER* force field and further optimizations using B3LYP/6-31+G* level. The study showed that septanoside ring in the trisaccharide adopted twist-chair conformation O,1TC5,6, as shown in Figure 1. Chapter 4 describes synthesis of septanoside containing di-and trisaccharides and conformational analysis of a 6-7-6 trisaccharide, through solution phase and computational methods. An effort was pursued to prepare septanoside-based amphiphiles with varying alkyl chain lengths, using our newly established methodology and to study their amphiphilicities. A series of septanoside amphiphiles, having C10 to C18 alkyl groups, were prepared as their -anomers as shown in Figure 2. The amphiphilic behavior of the alkyl septanosides was assessed through studies of their liquid crystalline (LC) properties. The LC properties were evaluated using polarizing optical microscopy, differential scanning calorimetry and powder X-ray diffraction methods. All the septanoside amphiphiles exhibited a smectic A phase in general. DSC thermograms showed crystal-crystal and crystal-mesophase phase transitions. Powder X-ray diffraction studies allowed to identify the lamellar structuring of the smectic A phase. Further, two distinct two layer spacings were observed. Such an observation is un-usual in carbohydrate liquid crystals. Chapter 5 details of synthesis and studies of the mesomorphic behavior of septanoside amphiphiles. In summary, the Thesis establishes a new route to synthesize septanoside derivatives, from oxyglycal sugar derivatives. Ring expansion of a pyranoside to a septanoside was achieved through key reactions of a cyclopropanation, ring opening, oxidation and reduction. Methyl α-D-glycero-septanoside derivatives were synthesized, from the corresponding oxyglycals. Cyclopropane ring opening ability of various nucleophiles were studied, it was found that ring-opening reactions with phenols, sugars, and azides are effective, which facilitated the synthesis of various aryl, glycosyl and azido-substituted septanosides. Synthesis of septanosides incorporated with di-and trisaccharides were accomplished. The detailed conformational analysis studies showed that the septanoside adopted twist-chair conformation in a trisaccharide molecule. Preparation and studies of septanoside based amphiphiles and their mesophase behavior were also accomplished. Overall, the studies presented in the Thesis provide a new insight to ring expanded sugars. The salient features of the present method are that the intermediates such as the seven membered vinyl halides, vinyl ethers, the diketones and the diols are potential sites for many other functionalizations. These features can be explored further in functionalizing the newly formed septanosides. (For structural formula pl see the pdf file)

In this thesis, carbohydrate mimicry is investigated through the syntheses of carbohydrate analogues and evaluation of their inhibitory effects on carbohydrate-processing enzymes. Galactofuranosides are interesting structures because they are common motifs in pathogenic microorganisms but not found in mammals. M.tuberculosis, responsible for the disease tuberculosis, has a cell wall containing a repeating unit of alternating (1→5)- and (1→6)-linked β-D-galactofuranosyl residues. Synthetic inhibitors of the enzymes involved in the biosynthesis of the cell wall could find great therapeutic use. The first part of this thesis describes the first synthesis of the hydrolytically stable carbasugar analogue of galactofuranose, 4a-carba-β-D-Galf, and the synthetic work of synthesising β-linked pseudodisaccharides containing carba-Galf, which were tested for glycosyltransferease inhibitory activity. The pseudodisaccharide carba-Galf-(β1→5)-carba-Galf was found to be a moderate inhibitor of the glycosyltransferase GlfT2 of M.tuberculosis. The thesis also describes how a general method towards biologically relevant α-linked carba-Galf ethers was developed. The final part of this thesis is focussed on the formation of nitrogen-linked monosaccharides without the participation of the anomeric centre. Such a mode of coupling is called tail-to-tail neodisaccharide formation. The couplings of carbohydrate derivatives via the Mitsunobu reaction are successfully reported herein. The method describes the key introduction of an allylic alcohol in the electrophile and the subsequent functionalisation of the alkene to obtain the neodisaccharide. Two synthesised neodisaccharides presented in this thesis have been sent to be tested for glycosidase inhibitory activity. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript. Paper 5: Manuscript. Paper 6: Manuscript.

A class of linear diamidines was synthesized for the evaluation as a treatment of Human African Trypanosomiasis. These fused heterocyclic compounds are thiazole[5,4-d]thiazoles and are of interest because the parent compound, 2,5-Bis(4-amidinophenyl)-thiazolo[5,4-d]thiazole HCl salt, which is also called DB 1929, has exhibited a low nanomolar IC50 value against Trypanosoma brucei rhodesiense and has shown selectivity for binding to the human telomere G-quadruplex over that of DNA duplex. A fluoro and a methoxy derivative have been synthesized and are currently undergoing testing for activity and binding affinity. In addition, fluorescence studies of selected diamidines were done to study the effect of structural variation on fluorescence. This data is useful since it can determine what types of moieties are needed to yield a compound that will fluoresce in the higher wavelengths (500 nm and above) of the visible spectrum, which would be advantageous in determining the uptake of the drug in the trypanosome within the endemic areas of Africa with a simple microscope.

Carbohydrates are ubiquitous and important biomolecules. Initially thought to be dull, energy storing moieties, the importance of carbohydrates and their conjugates, glycoproteins and glycopilids, in cellular communication and various related processes has been well established. Carbohydrate recognition events are involved in the progression of various diseases, as the binding of pathogens to the host cells is carbohydrate mediated. Also the malfunctioning of carbohydrate processing enzymes has been implicated in life-threatening diseases. Thus there is tremendous interest in the design of molecules which can mimic the carbohydrates and provide insights into the mechanisms of action of carbohydrate processing enzymes. Such designer glycomimics possess several advantages over the parent molecules. In this regard the synthesis of small molecules based on the polyhydroxylated cyclohexane framework has gained vital importance. Some of the efforts of several research groups actively working on the design and synthesis of glycomimics have culminated in therapeutics and resulted in the development of many synthetic routes to polyoxygenated cyclohexanoids emanating from either the chiral pool or from aromatics and other non-carbohydrate sources. Nevertheless, the design of a general and variable strategy to access these cyclohexitols is essential. Our quest for a general and more versatile strategy for accessing several of the polyoxygenated cyclohexanoids led to the development of a new norbornyl based approach. The important feature of our approach involves extraction of the inherent cyclohexanoid from the norbornyl scaffold. The present thesis entitled “Norbornyl system revisited: Exploring a versatile building block for the syntheses of natural products and analogues” delineates our synthetic endeavors. The thesis is represented in two parts “Part 1: Synthesis of polyoxygenated cyclohexanoids and azepanes” is subdivided into Introduction, Results and Discussion, Summary, Experimental, Spectra and References sections and describes our synthetic efforts towards various polyoxygenated cyclohexanoids and azepanes. Introduction deals briefly about the importance of glycomimics and synthetic approaches from the literature towards these polyhydroxylated cyclohexanoids. Our findings constitute the Results and Discussion section wherein we delineate the synthesis of a versatile cyclohexanoid building block through a Grob like Wharton fragmentation on an suitably crafted norbornyl scaffold. The synthetic utililty and versatility of this building block are explored in subsections titled Carbasugars, Cyclitols, Gabosines, Aminocyclitols and Azepanes. The synthesis of several polyhydroxylated cyclohexanoid natural products and analogues is discussed. “Part 2: Synthetic studies towards the novel diterpenoid rameswaralide” deals with the elaboration of the versatile norbornyl building block towards the synthesis of a novel 5-7-6 fused diterpenoid rameswaralide. This part is again divided into Introduction, Results and Discussion, Summary, Experimental, Spectra and References sections. The Introduction briefs the relevance and importance of total synthesis of natural products, with a mention of terpenoids. The structure and biological significance of rameswaralide and related molecules is discussed. In the Results and Discussion our synthetic studies towards rameswaralide are delineated. Restructuring the norbornyl framework to a 5,5 fused all cis Corey lactone and its further amplification through ring closing metathesis and Diels-Alder protocols are described.

Fluoreszenzfarbstoffe wurden über neuartige Palladium-katalysierte Domino-Reaktionen synthetisiert, die aus einer Sonogshira-Reaktion, zwei Carbopalladierungen und einer C-H-Aktivierung bestanden.

No description available.

Rotaxanes and porphyrins are two particularly active fields of research in chemistry. However,molecules that combine the interesting properties of these types of structures are not so common. In this thesis we describe new porphyrin-based multi-rotaxanes, whose syntheses constitute interesting challenges.Porphyrins linked to two or four coordinating macrocycles were synthesised. The "gathering-andthreading" effect of copper(I) was used to thread molecular rods through the rings; the subsequent introduction of stoppers led to the formation of rotaxanes. In the case of the porphyrinic bis-macrocycle a [4]rotaxane was obtained. Host/guest complexation studies with rigid nitrogen ligands showed that the rotaxane behaves as a distensible molecular receptor that can adopt an "inflated" or "deflated" conformation and adjust its shape to the size of the guest. In the case of the porphyrinic tetra-macrocycle the formation of a [3]rotaxane of novel architecture was observed.The synthesis of a new, more rigid bis-macrocycle is in progress. This compound will be used for the construction of a [4]rotaxane that could act as a molecular press able to change the conformation of a guest substrate by compression.

This thesis deals with the development and application of new synthetic methodology in organic chemistry. The first part describes the development of a new protocol for the synthesis of 3-pyrrolines by means of a microwave-assisted ring-expansion reaction of 2-vinylaziridines. In addition, this methodology is implemented as a key-step in a formal total synthesis of the antibiotic (-)-anisomycin. In the second part, a new methodology for the synthesis of arylglycines from Weinreb amides is described. In this procedure, a Grignard reagent is added to the iminium ion formed from the Weinreb amide upon treatment with a base. When a chiral amide is used, the nucleophilic addition proceeds with high diastereoselectivity. Finally, an easy and straightforward synthesis of α-amino amides via a base-mediated rearrangement of modified Weinreb amides into N,O-acetals is presented. Subsequent arylation, alkylation, alkenylation or alkynylation of this intermediate affords the corresponding α-amino amides in excellent yields. Furthermore, a more generalized protocol for the α-arylation of Weinreb amides lacking an α-amino moiety is also discussed. / QC 20100719

This thesis gives a detailed description of the design and synthesis of new organic sensitizers for Dye sensitized Solar Cells (DSCs). It is divided in 7 chapters, where the first gives an introduction to the field of DSCs and the synthesis of organic sensitizers. Chapters 2 to 6 deal with the work of the author, starting with the first publication and the other following in chronological order. The thesis is completed with some concluding remarks (chapter 7). The DSC is a fairly new solar cell concept, also known as the Grätzel cell, after its inventor Michael Grätzel. It uses a dye (sensitizer) to capture the incident light. The dye is chemically connected to a porous layer of a wide band-gap semiconductor. The separation of light absorption and charge separation is different from the conventional Si-based solar cells. Therefore, it does not require the very high purity materials necessary for the Si-solar cells. This opens up the possibility of easier manufacturing for future large scale production. Since the groundbreaking work reported in 1991, the interest within the field has grown rapidly. Large companies have taken up their own research and new companies have started with their focus on the DSC. So far the highest solar energy to electricity conversion efficiencies have reached ~12%. The sensitizers in this thesis are based on triphenylamine or phenoxazine as the electron donating part in the molecule. A conjugated linker allows the electrons to flow from the donor to the acceptor, which will enable the electrons to inject into the semiconductor once they are excited. Changing the structure by introducing substituents, extending the conjugation and exchanging parts of the molecule, will influence the performance of the solar cell. By analyzing the performance, one can evaluate the importance of each component in the structure and thereby gain more insight into the complex nature of the dye sensitized solar cell. / QC 20110505