This thesis describes stereoselective syntheses of four amino acids, three of which are C-glycosidic analogues of glycosylated amino acids. The overall goal of the project was to probe the interactions between MHC molecules, glycopeptide antigens and T cell receptors, that are essential for development of collagen induced arthritis. Collagen induced arthritis is a frequently used mouse model for rheumatoid arthritis, an autoimmune disease that attacks joint cartilage and leads to a painful and eventually crippling condition. The thesis is based on four studies. The first study describes the synthesis of hydroxylysine, an amino acid that is found in collagen and is an important constituent of the glycopeptide proposed as an antigen in collagen induced arthritis. During the synthesis of hydroxylysine some new insight into the mechanism of the reductive opening of p-methoxybenzylidene acetals was obtained. The remaining three studies deals with the synthesis of C-glycosidic analogues of glycosylated amino acids, hydroxy norvaline, threonine and hydroxylysine.The synthesis of each amino acid required control of several stereogenic centra and utilizes a variety of approaches such as use of stereoselective reactions, chiral auxilaries, chiral templates and asymmetric catalysis. The C-glycosidic analogues of galactosylated hydroxynorvaline and hydroxylysine were incorporated in glycopeptides from type II collagen and evaluated in T cell response assays. It was found that the T cells were stimulated by the C-glycopeptides, but that higher concentrations were required than for the native O-glycopeptide

This thesis deals with the design and syntheses of chiral,enantiopure pyridinecontaining ligands and their applicationsin asymmetric catalyis. Chiral pyridyl pyrrolidine ligands and pyridyl oxazolineligands were synthesized and employed in thepalladium-catalysed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate. Theinfluence of the steric properties of the ligands wereinvestigated. Ditopic ligands, containing crown ether units as structuralelements, were synthesized and some of the ligands were used asligands in the palladiumcatalysed allylic alkylation of1,3-diphenyl-2-propenyl acetate with dimethyl malonate. A smallrate enhancement was observed, compared with analogous ligandslacking the crown ether unit, when these ditopic ligands wereused in dilute systems. A modular approach was used to synthesize chiralenantiomerically pure pyridyl alcohols and C2-symmetric2,2’-bipyridines, with the chirality originating from thechiral pool. Electronic and steric properties of the compoundswere varied and they were used as ligands in theenantioselective addition of diethylzinc to benzaldehyde. Thesense of asymmetric induction was found to be determined by theabsolute configuration of the carbinol carbon atom. Theelectronic properties of the ligands had a minor influence onthe levels of enantioselectivity induced by the ligands. Chiral pyridyl phosphinite ligands and pyridyl phosphiteligands were synthesized from the pyridyl alcohols andevaluated as ligands in palladiumcatalysed allylic alkylations.With the phosphinite ligands, the sense of chiral induction wasfound to be determined by the absolute configuration of theformer carbinol carbon atom. A kinetic resolution of theracemic starting material was observed with one of thephosphite ligands. Moderate enantioselectivities wereachieved. <b>Kewords:</b>asymmetric catalysis, chiral ligand, chiralpool, oxazoline, crownether, ditopic receptor, bipyridine,pyridyl alcohol, modular approach, P,Nligand, diethylzinc,allylic alkylation.

This thesis deals with secondary interactions in asymmetric catalysis and their impact on the outcome of catalytic reactions. The first part revolves around the metal-catalyzed asymmetric allylic alkylation reaction and how interactions within the catalyst affect the stereochemistry. An OH–Pd hydrogen bond in Pd(0)–π-olefin complexes of hydroxy-containing oxazoline ligands was identified by density functional theory computations and helped to rationalize the contrasting results obtained employing hydroxy- and methoxy-containing ligands in the catalytic reaction. This type of hydrogen bond was further studied in phenanthroline metal complexes. As expected for a hydrogen bond, the strength of the bond was found to increase with increased electron density at the metal and with increased acidity of the hydroxy protons. The second part deals with the use of hydroxy- and methoxy-containing phosphinooxazoline ligands in the rhodium- and iridium-catalyzed asymmetric hydrosilylation reaction. The enantioselectivities obtained were profoundly enhanced upon the addition of silver salts. This phenomenon was explained by an oxygen–metal coordination in the catalytic complexes, which was confirmed by NMR studies of an iridium complex. Interestingly, the rhodium and iridium catalysts nearly serve as pseudo-enantiomers giving products with different absolute configurations. The final part deals with ditopic pyridinobisoxazoline ligands and the application of their metal complexes in asymmetric cyanation reactions. Upon complexation, these ligands provide catalysts with both Lewis acidic and Lewis basic sites, capable of activating both the substrate and the cyanation reagent. Lanthanide and aluminum complexes of these ligands were found to catalyze the addition of the fairly unreactive cyanation reagents ethyl cyanoformate and acetyl cyanide to benzaldehyde, whereas complexes of ligands lacking the Lewis basic coordination sites failed to do so. / QC 20100709

Chiral bisphosphinites are well-documented alternatives for chiral bisphosphines as ligands that can be exploited in various asymmpetric syntheses. Particularly, vicinal biarylphophinite ligands give a seven membered chelate ring similar to the successful DIOP on coordination to the metal. RajanBabu and coworkers have described asymmetric bisphosphinites obtained by functionalization of sugars and have shown their utility in enantioselective hydrogenation, hydrovinylation and hydrocynation reactions. Despite the interesting reactions demonstrated by bisphosphinites, not much attention has been paid to their synthesis and catalysis. This is probably due to the known moisture and oxygen sensitivity that makes their use limited. In the present thesis, a series of C1 an C2 symmetric bisphosphinite complexes of Pd(II) and Pt(II) have been synthesized directly from various naturally occurring chiral alcohols using a modified template method. A number of asymmetric catalytic reactions have been developed such as allylation of imines, allylation of aldehydes, allylic allylation, allylic alkylation, hydrosilylation of alkenes and regioselective allylation of oxiranes. Allylation of imines was carried out in essentially neutral conditions using Pd(II) catalysts and water was shown to accelerate the reaction. Interestingly acetic acid was required as a promoter in asymmetric allylation of cinnamaldehyde in the Pt(II) catalyzed reaction whereas water was a deterrent. Hydrosilylation reaction was carried out in solvent free conditions with high turnover numbers (.1000). Ascorbic acid based complexes produced the highest enantioselectivity for the asymmetric allylic alkylation reaction (97 % ee) and hydrosilylation of styrene (98% ee). These enantioselectivity results are the best obtained using ligands directly prepared from natural products.

<p>This thesis deals with the design and syntheses of chiral,enantiopure pyridinecontaining ligands and their applicationsin asymmetric catalyis.</p><p>Chiral pyridyl pyrrolidine ligands and pyridyl oxazolineligands were synthesized and employed in thepalladium-catalysed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate. Theinfluence of the steric properties of the ligands wereinvestigated.</p><p>Ditopic ligands, containing crown ether units as structuralelements, were synthesized and some of the ligands were used asligands in the palladiumcatalysed allylic alkylation of1,3-diphenyl-2-propenyl acetate with dimethyl malonate. A smallrate enhancement was observed, compared with analogous ligandslacking the crown ether unit, when these ditopic ligands wereused in dilute systems.</p><p>A modular approach was used to synthesize chiralenantiomerically pure pyridyl alcohols and C2-symmetric2,2’-bipyridines, with the chirality originating from thechiral pool. Electronic and steric properties of the compoundswere varied and they were used as ligands in theenantioselective addition of diethylzinc to benzaldehyde. Thesense of asymmetric induction was found to be determined by theabsolute configuration of the carbinol carbon atom. Theelectronic properties of the ligands had a minor influence onthe levels of enantioselectivity induced by the ligands.</p><p>Chiral pyridyl phosphinite ligands and pyridyl phosphiteligands were synthesized from the pyridyl alcohols andevaluated as ligands in palladiumcatalysed allylic alkylations.With the phosphinite ligands, the sense of chiral induction wasfound to be determined by the absolute configuration of theformer carbinol carbon atom. A kinetic resolution of theracemic starting material was observed with one of thephosphite ligands. Moderate enantioselectivities wereachieved.</p><p><b>Kewords:</b>asymmetric catalysis, chiral ligand, chiralpool, oxazoline, crownether, ditopic receptor, bipyridine,pyridyl alcohol, modular approach, P,Nligand, diethylzinc,allylic alkylation.</p>

No description available.

Récemment, de nombreux efforts ont été consacrés au développement d'oligonucléotides synthétiques pour des applications thérapeutiques et de diagnostique variées. Les oligonucléotides modifiés peuvent inhiber sélectivement l'expression des gènes en se liant spécifiquement à des séquences d'ADN et/ou d'ARN ciblées à travers les stratégies antigène, antisens ou d'ARN interférent. Les aminoxy peptides forment facilement des structures secondaires bien définies comme des alpha-, béta-, gamma-turns ou des hélices, ce qui nous a inspiré pour concevoir de nouveaux oligonucléotides modifiés dans le but d'étudier leurs propriétés physico-chimiques et biologiques. Au cours de ce travail, la synthèse de nucléosides aminoxy acides et de leurs oligomères a été entreprise en séries ribose et désoxyribose. Dans la première partie, les fonctions aminoxyle, acide carboxylique et aldéhyde ont été introduites sur la partie osidique de la thymidine. Différents nucléosides monofonctionnalisés ont été synthétisés à l'aide notamment des réactions de Mitsunobu, d'O-allylation et d'oxydation. Les nucléosides monomères ont ensuite été couplés entre eux conduisant aux nouveaux dinucléosides liés par liaison N-oxy amide, oxime et aminoxy. Dans la seconde partie, la synthèse de différentes uridines aminoxy acides a été étudiée à partir de l'uridine, des 2,2'-anhydro et 2,3'-anhydro uridines. Une uridine aminoxy ester a pu être obtenue en passant par la 3'-oxo uridine via une homologation (réaction de Wittig) et l'introduction de la fonction oxyamine en position 5' par une substitution nucléophile du dérivé iodé. En parallèle, dans la continuité des travaux réalisés au laboratoire sur la synthèse des glycoamino acides, nous avons synthétisé des C-glycosyl aminoxy acides jamais décrits dans la littérature, dans le but de générer de nouveaux mimes de glycopeptides. A partir du C-allyl glucopyranoside perbenzylé, deux C-glucosyl aminoxy acides diastéréoisomères ont été préparés.

This work presents the synthesis of three new series of nitrogen-heterocycles containing the substituent trifluoromethyl, exploiting the synthetic versatility and regioselectivity of 4-alkoxy-5-bromo-1,1,1-trifluorpent-3-en-2-ones and 4-amino-5-bromo-1,1,1-trifluoropent-3-en-2-ones in reactions with compounds containing nucleophilic nitrogen. Two series of 1-(3-alkoxy-5-trifluoromethyl-2,3-dihydrofuran-3-yl)-4,5-alkyl-3-(trifluoromethyl)-1H-pyrazoles were synthesized by the N-functionalization reaction of pyrazoles with 4-alkoxy-5-bromo-1,1,1-trifluorpent-3-en-2-ones, by Michael s nucleophilic addition. In the first step, there is a nucleophilic addition of the pyrazol molecule to the beta position of enones (Cβ), followed by an intramolecular cyclization reaction, where the furan ring is formed by replacement of the bromine atom by the carbonyl oxygen of enone, resulting in thirteen novel compounds with yields between 55-86%. The other compounds series, (E)-4-(amino)-1,1,1-trifluoro-5-(5-methyl-3- (trifluoromethyl)-1H-pyrazol-1-yl)pent-3-en-2-ones, was synthesized by N-alkylation reaction, through a bimolecular nucleophilic substitution (SN2) mechanism, with replament of the bromine atom, at five position (Cγ) of 4-amino-5-bromo-1,1,1-trifluoropent-3-en-2-ones, by the nucleophilic nitrogen of the pyrazoline ring. Seven N-alkylated products were obtained, with yields among 65-85%. In addition, the regioselectivity study of N-functionalized pyrazoles reactions is described, including the evaluation of reaction conditions and how substituents present in the pyrazole structure can influence the product formation, because many different steric and electronic factors. The obtained compounds were characterized by nuclear magnetic resonance 1H and 13C, mass spectrometry, elementary analysis and X-ray diffractometry. / A presente dissertação relata a síntese de três séries inéditas de heterociclos nitrogenados trifluormetil substituídos, que exploram a versatilidade sintética e a regiosseletividade das 4-alcóxi-5-bromo-1,1,1-trifluorpent-3-en-2-onas e das 4-amino-5-bromo-1,1,1-trifluorpent-3-en-2-onas, em reações com nucleófilos nitrogenados. As primeiras duas séries dos compostos 1-(3-alcóxi-5-trifluorometil-2,3-diidrofuran-3-il)-4,5-alquil-3-(trifluorometil)-1H-pirazóis, foram sintetizadas através do processo de N-funcionalização de pirazóis, a partir da reação com as 4-alcóxi-5-bromo-1,1,1-trifluorpent-3-en-2-onas, cujo o caminho mecanístico se deu através de uma reação de adição nucleofílica de Michael. Inicialmente, ocorre a adição do pirazol nucleofílico na posição beta (Cβ) das enonas bromadas, seguida de uma reação de ciclocondensação intramolecular formando o anel furano, com a substituição átomo de bromo pelo oxigênio enólico, resultando na formação de treze compostos inéditos, com rendimentos entre 55 e 86%. Outra série de compostos (E)-4-(amino)1,1,1-triflúor-5-(5-metil-3-(trifluormetil)-1H-pirazóis-1-il)pent-3-en-2-onas, foi sintetizada através da reação de N-alquilacão, via substituição nucleofílica bimolecular (SN2), onde o átomo de bromo na posição cinco (Cγ), das 4-amino-5-bromo-1,1,1-trifluorpent-3-en-2-onas, foi substituído pelo nitrogênio nucleofílico do anel pirazolínico, promovendo a formação de sete produtos N-alquilados, com rendimentos que variam entre 65 e 85%. Além disso, um estudo de regiosseletividade das reações N-funcionalizadas de pirazóis está descrito, onde a avaliação das condições reacionais e também de fatores estéricos e eletrônicos dos substituintes presentes nos substratos, foram determinantes para formação do produto formado. Os produtos obtidos neste trabalho foram caracterizados por ressonância magnética nuclear de 1H e 13C, espectrometria de massas de baixa e alta resolução, análise elementar e difratometria de Raio X.

The thesis entitled “Organocatalytic Cascade Cyclizations for the Enantioselective Synthesis of Spirooxindoles” is divided into three chapters. Chapter 1: Catalytic Enantioselective Michael Addition/Cyclization Cascade of 3-Isothiocyanato Oxindoles with Nitroolefins A myriad of spirocyclic frameworks present in natural product, and pharmaceutically important compounds, has attracted the synthetic organic chemists to explore their preparation in enantioselective manner. Consequently various strategies have been devised for efficiently accessing highly functionalized spirooxindoles. Among these strategies, the use of 3-isothiocyanato oxindoles as the building block appeared as the most popular one. The combination of 3-isothiocyanato oxindoles and a variety of electrophiles have already been reported. However one of the most popular electrophiles, nitroolefins, has never been used in the reaction with 3-isothiocyanato oxindoles. In this chapter, a highly efficient catalytic asymmetric Michael addition/cyclization cascade reaction between 3-isothiocyanato oxindoles and β-substituted nitroolefins with the help of a cinchonidine-derived bifunctional thiourea catalyst has been discussed. Highly functionalized spirooxindoles containing three successive stereocenters were obtained in high yield with moderate to good diastereo- and enantioselectivity. Reference: Kayal, S.; Mukherjee, S. Eur. J. Org. Chem. 2014, 6696-6700. Chapter 2: Catalytic Aldol-Cyclization Cascade of 3-Isothiocyanato Oxindoles with α-Ketophosphonates for the Enantioselective Synthesis of β-Amino-α-Hydroxyphosphonates The oxindole scaffold containing a quaternary stereocenter at the C3 position is a privileged structural motif present in many biologically active molecules and natural products. In this respect, spirooxindoles have received special attention during the past few years. Similarly, β-Amino and/or hydroxy functionalized phosphonic acids and their derivatives are found to display inhibitory activities towards a range of enzymes such as renin, HIV protease, thrombin, and various classes of protein tyrosine kinases and phosphatases. Considering the importance of both oxindole and β-amino-α-hydroxyphosphonic acid, we reasoned that highly functionalized phosphonic acid derivatives based on a spirooxindole framework could be of potential biological significance, if synthesized in enantiopure form This chapter deals with a cascade aldol-cyclization reaction between 3-isothiocyanato oxindoles and α-ketophosphonates for the enantioselective synthesis of spirooxindole-based β-amino-α-hydroxyphosphonate derivatives. Catalyzed by cinchona alkaloid-based bifunctional thiourea derivatives, this protocol delivers 2-thioxooxazolidinyl phosphonates bearing two adjacent quaternary stereogenic centers, generally in high yields with excellent diastereo- and enantioselectivities. Both the product enantiomers are accessible with nearly equally high level of enantioselectivity. Reference: Kayal, S.; Mukherjee, S. Org. Lett. 2015, 17, 5508-5511. Chapter 3: Catalytic Michael Addition/Cyclization Cascade of 3-Isothiocyanato Oxindoles with Cyclic α,β-Unsaturated Ketones: A Concise Enantioselective Synthesis of Bispiro[indoline-3,2'-pyrrolidine] Among different spirocyclic cores, the spirooxindole framework containing pyrrolidinyl ring represents a very important class owing to their biological activities such as antimicrobial, anticancer, antihypertensive, antidiabetic, antimycobacterial and antitubercular properties. Similarly, the bispirooxindole scaffold recently has drawn considerable interests because of its exclusive structural and stereochemical diversity. Only a few examples have been reported till date for enantioselective construction of the pharmaceutically important bispirooxindole architectures. Considering the importance of bispirooxindoles and pyrrolidinyl spirooxindole scaffolds, we were interested in merging them in a single molecular framework. In this chapter, a Michael addition/cyclization cascade reaction between 3-isothiocyanato oxindoles and exocyclic enones for the enantioselective synthesis of 3,2′-pyrrolidinyl bispirooxindole derivatives has been illustrated. With the help of a quinine-derived bifunctional squaramide as the catalyst, this protocol delivers bispirooxindoles bearing three contiguous stereogenic centers, in high yields and generally with outstanding diastereo- and enantioselectivity. Reference: Kayal, S.; Mukherjee, S. manuscript under preparation.

The thesis entitled “Total synthesis of bio-active macrolide natural products and sulphonamide based ligands in asymmetric catalysis” is divided into two chapters. First chapter of the thesis describes the total synthesis of bio-active macrolide natural products cladospolide A 1, seimatopolide A 2 and synthetic studies towards aetheramides A 3 and B 4 (Figure 1). Figure 1: Bio-active macrolide natural products. Section A of chapter 1 describes the enantiospecific total synthesis of cladospolide A (ent-1). Cladospolide A was isolated from three different sources such as culture filtrate of cladosporium fulvam FI-113, Fungus cladosporium tenuissimum and Fermentation broath of cladosporium sp. FT-0012. Cladospolide A is shown to inhibit the root growth of lettuce seedlings. Enantiospecific total synthesis of cladospolide A ent-1 was accomplished in 9% overall yield in 11 linear steps using D-ribose as a chiral pool precursor. Key reactions in the present approach include olefin cross metathesis and Yamaguchi macrolactonization reactions (Scheme 1). Scheme 1: Total synthesis of cladospolide A (ent-1). Section B of chapter 1 describes the use of furan as a surrogate for the E-but-2-ene-1, 4-dione unit in the total synthesis of seimatopolide A 2. Seimatopolide A 2 was isolated by Heip and co-workers from the fungus Seimatosporium discosioides in 2012 and is shown to activate the γ-subtype peroxysome proliferator-activated receptors (PPAR-γ), which is a pivotal process in the type-2 diabetes. Total synthesis of ent-seimatopolide A was accomplished in 7.8% overall yield in 14 linear steps from furfural. Nagao acetate aldol and Shiina macrolactonization reactions were employed as key reactions for the synthesis of ent-seimatopolide A (ent-2) (Scheme 2). Scheme 2: Stereoselective total synthesis of seimatopolide A (ent-2). In section C of Chapter 1, studies towards the synthesis of aetheramides A 3 and B 4 are described. Aetheramides A 3 and B 4 are isolated by Müller’s group in 2012 from the novel myxobacterial genus “Aetherobacter”. Aetheramides are cyclic depsipeptides, which are shown to inhibit the HIV-I infection with IC50 values of ∼0.015 μM and cytostatic activity against human colon carcinoma (HCT-116) cells with IC50 values of 0.11 μM. Stereochemistry at two chiral centers present in the molecules is unassigned. The first approach (Scheme 3) relied on macrolactonization as the key step while the second approach (Scheme 4) relied on RCM to accomplish the macrolactonization. The required precursors were synthesized from elaboration of chiral furyl carbinol, while synthesis of the RCM precursor was accomplished employing the aldol reaction. Scheme 3: Macrolactonization strategy for synthesis of 3 from chiral furyl carbinol. Scheme 4: RCM strategy for synthesis of 3 from chiral furyl carbinol. The successful synthesis of the macrolactone core of aetheramide A 1 is accomplished by employing the ring closing metathesis reaction to construct the C18-C19 bond. RCM precursor has been synthesized by the amidation of the amine derived from R-mandelic acid, while the acid fragment is synthesized from allyl trityl ether (Scheme 5). Scheme 5: RCM strategy for synthesis of 3 from R-mandelic acid. Second chapter of the thesis describes the synthesis and application of novel sulfinamide ligands in asymmetric catalysis. In section A of chapter 2, chiral 2-pyridylsulfinamides are shown to be effective catalysts in the alkylation of aryl and alkyl aldehydes with diethylzinc providing the corresponding alcohols in excellent enantioselectivity. It was found that the chirality present at sulfur in the ligand is pivotal for the asymmetric induction (Scheme 6). Scheme 6: Asymmetric alkylation of benzaldehyde with some of the 2-Pyridyl sulfinamide catalysts. Second section of chapter 2 describes the synthesis and application of C2-symmetric bis-sulfinamides in Rh (I) catalyzed conjugate addition of PhB(OH)2 to enones. Chirality present at sulphur in sulfonamide as well as symmetry present in the ligand plays crucial role in the outcome of the reaction (Scheme 7). Scheme 7: Asymmetric arylation of enones using C2-symmetric bis-sulfinamide/olefin ligands. The thesis entitled “Total synthesis of bio-active macrolide natural products and sulphonamide based ligands in asymmetric catalysis” is divided into two chapters. First chapter of the thesis describes the total synthesis of bio-active macrolide natural products cladospolide A 1, seimatopolide A 2 and synthetic studies towards aetheramides A 3 and B 4 (Figure 1). Figure 1: Bio-active macrolide natural products. Section A of chapter 1 describes the enantiospecific total synthesis of cladospolide A (ent-1). Cladospolide A was isolated from three different sources such as culture filtrate of cladosporium fulvam FI-113, Fungus cladosporium tenuissimum and Fermentation broath of cladosporium sp. FT-0012. Cladospolide A is shown to inhibit the root growth of lettuce seedlings. Enantiospecific total synthesis of cladospolide A ent-1 was accomplished in 9% overall yield in 11 linear steps using D-ribose as a chiral pool precursor. Key reactions in the present approach include olefin cross metathesis and Yamaguchi macrolactonization reactions (Scheme 1). Scheme 1: Total synthesis of cladospolide A (ent-1). Section B of chapter 1 describes the use of furan as a surrogate for the E-but-2-ene-1, 4-dione unit in the total synthesis of seimatopolide A 2. Seimatopolide A 2 was isolated by Heip and co-workers from the fungus Seimatosporium discosioides in 2012 and is shown to activate the γ-subtype peroxysome proliferator-activated receptors (PPAR-γ), which is a pivotal process in the type-2 diabetes. Total synthesis of ent-seimatopolide A was accomplished in 7.8% overall yield in 14 linear steps from furfural. Nagao acetate aldol and Shiina macrolactonization reactions were employed as key reactions for the synthesis of ent-seimatopolide A (ent-2) (Scheme 2). Scheme 2: Stereoselective total synthesis of seimatopolide A (ent-2). In section C of Chapter 1, studies towards the synthesis of aetheramides A 3 and B 4 are described. Aetheramides A 3 and B 4 are isolated by Müller’s group in 2012 from the novel myxobacterial genus “Aetherobacter”. Aetheramides are cyclic depsipeptides, which are shown to inhibit the HIV-I infection with IC50 values of ∼0.015 μM and cytostatic activity against human colon carcinoma (HCT-116) cells with IC50 values of 0.11 μM. Stereochemistry at two chiral centers present in the molecules is unassigned. The first approach (Scheme 3) relied on macrolactonization as the key step while the second approach (Scheme 4) relied on RCM to accomplish the macrolactonization. The required precursors were synthesized from elaboration of chiral furyl carbinol, while synthesis of the RCM precursor was accomplished employing the aldol reaction. Scheme 3: Macrolactonization strategy for synthesis of 3 from chiral furyl carbinol. Scheme 4: RCM strategy for synthesis of 3 from chiral furyl carbinol. The successful synthesis of the macrolactone core of aetheramide A 1 is accomplished by employing the ring closing metathesis reaction to construct the C18-C19 bond. RCM precursor has been synthesized by the amidation of the amine derived from R-mandelic acid, while the acid fragment is synthesized from allyl trityl ether (Scheme 5). Scheme 5: RCM strategy for synthesis of 3 from R-mandelic acid. Second chapter of the thesis describes the synthesis and application of novel sulfinamide ligands in asymmetric catalysis. In section A of chapter 2, chiral 2-pyridylsulfinamides are shown to be effective catalysts in the alkylation of aryl and alkyl aldehydes with diethylzinc providing the corresponding alcohols in excellent enantioselectivity. It was found that the chirality present at sulfur in the ligand is pivotal for the asymmetric induction (Scheme 6). Scheme 6: Asymmetric alkylation of benzaldehyde with some of the 2-Pyridyl sulfinamide catalysts. Second section of chapter 2 describes the synthesis and application of C2-symmetric bis-sulfinamides in Rh (I) catalyzed conjugate addition of PhB(OH)2 to enones. Chirality present at sulphur in sulfonamide as well as symmetry present in the ligand plays crucial role in the outcome of the reaction (Scheme 7). Scheme 7: Asymmetric arylation of enones using C2-symmetric bis-sulfinamide/olefin ligands.