Metal-catalyzed cyclopropanation on the 8-oxabicyclo[3.2.1]oct-6-ene template

Cyclopropanations of an 8-oxabicyclo[3.2.1]octene substrate using diazocarbonyl compounds provided exo, exo-cyclopropanated products as the sole or major diastereomeric oxatricyclic products. Reductive cleavage of a meso-oxatricyclic ketone by samarium iodide resulted in desymmetrization without concomitant oxygen bridge cleavage. © 2005 Elsevier Ltd. All rights reserved.postprin

Studies on Reactions of Cyclopropanated Pyrrole: Synthesis of Bis-β-homoproline, Tropane- and Pyrrolidinone-derivatives

Cyclopropanated pyrroles have been accompanied in lots of reactions due to its versatility and capability to approach to more complex molecules. The unique reactivity of cyclopropanated pyrroles results from the three-membered ring which has a tendency to release the ring strain and the substituents around it to provide the electronic characteristics. As described in first chapter in the main part, the dimerization of cyclopropanated pyrrole 60c was catalyzed by the hidden Brønsted acid generated from the gold catalyst and phenylacetylene. Under such mild condition, dimer 121 was obtained as a single diastereomer in a good yield which could be then straightforwardly transformed into bis-β-homoproline 146 after hydrogenation, ring opening and deprotection. The synthesis of enantiopure 146 and the evaluation of its activity as an organocatalyst are still to be explored. Next in second chapter, cycloaddition of substrate 60b and 60d has been investigated. The cycloaddition reaction utilized 1,3-dipole generated in-situ from substrate 60d under heating condition which was then reacted with various dipolarophiles. The reaction could occur without a catalyst and by simple procedure, the desired tropane products could be obtained stereoselectively in high yields. Further functionalizations to get access to cocaine or ferruginine derivatives are currently ongoing in the working group. In the last chapter, the literature known procedure for enantioselectie pyrrolidinone synthesis has been employed to the substrate 249. In order to generate chiral 249, an asymmetric rhodium-catalyzed cyclopropanation was performed which was followed by bromohydrin formation and subsequent oxidation to afford the intermediate 257. In the end, chiral pyrrolidinone 258 and 259 were obtained by radical ring opening reaction with AIBN and n-Bu3SnH. All of performed reactions has shown to retain high enantiopurity of intermediates and products. In summary, three different applications of cyclopropanated pyrrole 60 have been explored and demonstrated. From bis-β-homoproline 146 to tropane- (197) and pyrrolidinone-derivative (258 and 259), such complex compounds could be successfully synthesized from substrate 60 and high stereoselectivity could be achieved in all transformations

Borane-ctalyzed stereoselective C–H insertion, cyclopropanation, and ring-opening reactions

Lewis acidic boranes have been shown to be effective metal-free catalysts for highly selective reactions of donor-acceptor diazo compounds to a range of substrates. The reactions of α-aryl α-diazoesters with nitrogen heterocycles indole or pyrrole selectively generate C3 and C2 C–H insertion products, respectively, in good to excellent yields even when using unprotected indoles. Alternatively, benzofuran, indene, and alkene substrates give exclusively cyclopropanated products with α-aryl α-diazoesters, whereas the reactions with furans lead to ring-opening. Comprehensive theoretical calculations have been used to explain the differing reactivities and high selectivities of these reactions. Overall, this work demonstrates the selective metal-free catalytic reactions of α-aryl α-diazoesters with (hetero)cycles and alkenes. This simple, mild reaction protocol represents an alternative to the commonly used precious metal systems and may provide future applications in the generation of biologically active compounds

1,5-Anhydro-2-de­oxy-1,2-C-dichloro­methyl­ene-3,4,6-tri-O-(4-meth­oxy­benz­yl)-d-glycero-d-gulo-hexitol

The pyranosyl ring in the title compound, C31H34Cl2O7, adopts a twist-boat conformation. The 4-meth­oxy­benzyl groups are located in equatorial positions with the meth­oxy groups nearly coplanar with their respective rings [dihedral angles of 0.2 (3) and 9.4 (2)°]. The aromatic rings adopt orientations enabling them to participate in C—H⋯π inter­actions with neighboring meth­oxy groups. The crystal structure is additionally stabilized by weak C—H⋯O inter­actions

METABOLIC NETWORK ANALYSIS OF MYCO-BACTERIUM TUBERCULOSIS (MTB)

Tuberculosis is a multisystem disorder that is characterized by the formation of hematomas, a type of swelling that is filled with blood that is caused due to breakage in the wall of a blood vessel. This hematomas occurs in different organ of the infected victim has claimed the life of most of its victims. This disease is caused by a bacterium known as Mycobacterium Tuberculosis (MTB) which can be represented as a metabolic system. Every biological system is made up a metabolites which include genes, proteins and enzymes that are inter-connected which define the function, features and characteristics of the biological system. These biological systems can be analysed using different computational techniques among which is flux balance analysis. Flux balance analysis is a constraint based approach to metabolic network analysis. It’s based on the steady state assumption of S.v = 0. A more grounded understanding of this features, characteristics and nature of this bacterium will lead to better approaches to reduce the damage of the disease. The flux balance analysis of MTB involves the conversion of the metabolic network into a matrix format known as a stoichiometric matrix. This matrix is formed by using the metabolites in the metabolic network as rows and the reactions as the columns. The stoichiometric matrix used in this research is an 828 by 1027 matrix. The analysis of the stoichiometric matrix resulted into a linear problem where the number of unknown is greater than the number of equations. This linear problem was solved using “extreme pathways” and “simplex method” algorithms which makes up a Flux Balance Analysis approach to metabolic network analysis. The extreme pathways algorithm help extract the independent paths in the network while the simplex method is used to optimize the metabolic network to extract metabolites peculiar to an objective function. 15 At applying the constraint of the steady state assumption, the result showed 1022 distinct pathways instead of the initial 1027 eliminating 5 other reactions. The output from the extreme pathways was used in the optimization process using biomass as the target flux to get metabolites peculiar to biomass production. After the optimization, the result shows 32 new metabolites that become activated when a value of 1 is used to represent the biomass components. The optimization result also shows two categories of metabolites: those that are part of the biomass that become inactive after optimization, those that remain active after the optimization test. The output of this research only focus on the analysis of the metabolic network using biomass as the optimization target

Catalytic cyclopropanation of polybutadienes

Catalytic cyclopropanation of commercial 1,2- or 1,4- cis -polybutadiene, respectively, with ethyl diazoacetate catalyzed by [Tp Br3 Cu(NCMe)] (Tp Br3 ¼ hydrotris(3,4,5-tribromo-1-pyrazo- lyl)borate) at room temperature afforded high molecular weight ( M n > 10 5 mol 1 ) side-chain or main-chain, respectively, carbox- yethyl cyclopropyl-substituted polymers with variable and con- trolled degrees of functionalization. Complete functionalization of 1,4- cis -polybutadiene afforded poly[ethylene-alt-(3-ethoxycar- bonyl-cyclopropene)]. Catalytic hydrogenation of residual dou- ble bonds of partially cyclopropanated polybutadienes provided access to the corresponding saturated polyolefins. Thermal properties are reported.MICINN CTQ2008-00042BQU MICINN HA2004-0067 Junta de Andalucia P05-FQM091

Borane-Catalyzed Stereoselective C–H Insertion, Cyclopropanation, and Ring-Opening Reactions

Lewis acidic boranes have been shown to be effective metal-free catalysts for highly selective reactions of donor-acceptor diazo compounds to a range of substrates. The reactions of α-aryl α-diazoesters with nitrogen heterocycles indole or pyrrole selectively generate C3 and C2 C–H insertion products, respectively, in good to excellent yields even when using unprotected indoles. Alternatively, benzofuran, indene, and alkene substrates give exclusively cyclopropanated products with α-aryl α-diazoesters, whereas the reactions with furans lead to ring-opening. Comprehensive theoretical calculations have been used to explain the differing reactivities and high selectivities of these reactions. Overall, this work demonstrates the selective metal-free catalytic reactions of α-aryl α-diazoesters with (hetero)cycles and alkenes. This simple, mild reaction protocol represents an alternative to the commonly used precious metal systems and may provide future applications in the generation of biologically active compounds