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Cyclic oligomers in macromolecular and supramolecular chemistryZhu, Zhixue January 2003 (has links)
No description available.
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The development of enantioselective receptors for amino acid derivativesShepherd, Emma J. January 2000 (has links)
No description available.
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Early transition metal imido complexes supported by heterocyclic ligandsWilson, Paul John January 1999 (has links)
No description available.
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FOLDAMERS AND MACROCYCLES BASED ON FORMAMIDOXIME SUBUNITSZHAO, WEIWEN 10 August 2011 (has links)
The objective of this thesis is the study of the control of the shape of formamidine motifs and application to folding open-ended structures and more elaborate macrocycles.
The multi-step synthesis of macrocycles M1 and M2, which are analogs of 18-crown ether-6, have been successfully achieved. Macrocycles M1 and M2 have been fully characterized. The study of the crystal structures of M1 and M2 gave interesting information about their packing and molecular recognition properties.
Moreover, analysis of some by-products formed in macrocyclizations gave intriguing results. The existence of a four-pyridine-unit interlocked catenane which was isolated from the synthesis of M1 has been confirmed by MS-MS. A surprisingly large 54-membered macrocycle “Maxi-M2” was isolated from the synthetic crude product of M2 and confirmed by X-ray crystallography.
Driven by the desire to understand the formation of catenane and “Maxi-M2”, a systematic study of the corresponding condensation reaction was performed. The E isomers derived from N-acyl-N’-substituted formamidoximes were, for the first time, reported and isolated. The protons can facilitate E to Z isomerization. The best conditions to selectively generate either the E or Z isomers have been fully studied and applied to the synthesis.
The unexpected formation of the E isomers may promote polymerization and limit the yield improvement of macrocyclization. Therefore, a new synthetic method for the target macrocycle M2 was investigated, trying to avoid the formation of E isomers and thus cyclize more efficiently. / Thesis (Master, Chemistry) -- Queen's University, 2011-08-05 14:48:21.156
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Development of macrocyclic β-strand calpain cysteine protease inhibitorsChen, Hongyuan January 2011 (has links)
The work in this thesis reports studies directed to developing a calpain cysteine protease
inhibitor that could be of value in slowing cataract development in humans. The work
focuses on the development of macrocyclic compounds which can have advantages over
acyclic compounds due to their resistance to proteolytic hydrolysis, improved selectivity,
bioavailability and membrane permeability. A review of X-ray crystal structures of
natural and synthetic calpain inhibitors complexed with the cysteine protease calpain
show the inhibitors generally bind in the enzyme active site in an extended β-strand
conformation.
The calpain inhibitor SJA-6017 has been identified as a suitable lead compound. The
importance of the para-fluoro group in SJA-6017 has been investigated. Modifications
have been made to constrain this basic structure within a macrocycle and restrict the
peptide chain as a β-strand conformation. Macrocycle CAT811 is a potent calpain 1 and
2 inhibitor and shows promise in slowing the progression of cortical cataract in trials with
sheep having a hereditary propensity towards the development of cataract.
In this thesis I report studies directed to improve the yield of the key RCM
macrocyclisation step in the synthesis of aldehyde CAT811 and of three ester analogues
(2.1, 2.3 and 2.4).
I also report the development of a more commercial route to CAT811 not involving
RCM but using intramolecular nucleophilic cyclisation.
This intramolecular nucleophilic cyclisation strategy was attempted for the preparation of
a histidine containing macrocyclic ester (4.1a) but was unsuccessful. An alternate
strategy involving intramolecular lactamization proved successful for the synthesis of
histidine-based macrocyclic esters (4.1a-4.3a). Reduction to the corresponding alcohols
(4.1b-4.3b) was successful and oxidation of (4.1b and 4.3b) afforded the corresponding
aldehydes (4.1c and 4.3c) for biological assay against ovine calpain 2.
Aldehyde 4.3c has an IC50 of 1 μM and the corresponding alcohol 4.3b shows no activity
(IC50 > 50 μM) consistent with the modelling which indicated that these two compounds
did not adopt a β-strand conformation in the docking studies. Aldehyde 4.1c, on the other
hand, shows significant inhibitory activity with an IC50 of 238 nM but as expected the
corresponding alcohol 4.1b shows little activity (IC50 = 29 μM). Modelling studies
showed that both the aldehyde 4.1c and the alcohol 4.1b on docking can form a β-strand
with appropriate H-bonding interactions. The aldehyde is more active than the alcohol
due to the reactivity of the aldehyde warhead allowing for the reversible formation of a
hemiacetal. A similar difference in reactivity is observed for CAT811 (30 nM) and its
alcohol analogue (700 nM).
These results demonstrate the value of molecular modelling as a screening mechanism
before unproductive synthetic work is considered.
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Harnessing Natural Product Biosynthesis to Access MacrocyclesHeberlig, Graham William 30 May 2019 (has links)
Macrocyclic natural products are conformationally restricted molecules that often have improved ability to bind with high affinity and selectivity on a target. Within macrocycle chemistry, macrolactone formation is a particularly challenging transformation and has spurred the development of highly diverse synthetic strategies. A key strategy that is missing is a chemoenzymatic approach to this challenge, and the logical place to look for such a catalyst is the thioesterases (TEs) from the biosynthetic pathways that generate these molecules in Nature. These TEs are α/β-hydrolases containing an active site serine or cysteine and a conserved histidine/aspartate catalytic diad. The research presented here describes the development of two related TE domains from resorcylic acid lactone polyketide synthases found in various fungi. Unlike their bacterial counterparts these macrocyclization catalysts have proven to be stereotolerant with regard to the secondary alcohols involved in macrocyclization. Further work has demonstrated that they are also amenable to generating 12- to 18-member macrolactones. These TE domains can also catalyze macrolactam and cyclic depsipeptide formation, setting the stage for these enzymes to serve as a platform for catalyst development. The development of 2,3-diaminopropionate (DAP) incorporation in place of the active site Ser to trap acyl-enzyme intermediates was used to structurally characterize the formation of a macrocyclic trimer. This technique will be broadly applicable to characterizing other TEs. Overall the research presented here lays the foundation for the long term development of TEs as macrocyclization biocatalysts.
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Synthesis and study of photoswitchable glycomacrocycles / synthèse et étude de glycomacrocycles photocommutablesLin, Chaoqi 30 October 2018 (has links)
Grace à leur excellente propriété photochromique, les dérivés d’azobenzène trouvent de plus en plus d’applications pour le photocontrôle spatio-temporel de conformations moléculaires, de réactivités chimiques, des activités biologiques et pharmaceutiques. Dans ce contexte, introduire un motif photochromique dans les macrocycles contenant de glucides représente une approche excitante afin de moduler par la lumière les propriétés physicochimiques, chimiques et biologiques de cette unique classe de molécules qui attirent d’attention croissante en chimie médicinale et en science des matériaux.Deux séries de glycomacrocycles photocommutables ont été synthétisés dans cette thèse. La première est obtenue via une approche d’O-alkylation en one-pot, à partir 2,2’-dihydroxyazobenzène et di-O-bromoacétyl glycosides. Ces glycomacrocycles possèdent d’excellentes propriétés photochromiques, avec une haute résistance à la fatigue. Le transfert de chiralité de glucide à l’azobenzène a été observé. L’un des glycomacrocycles est capable de former d’organogels qui répond aux stimuli photo, thermique et mécanique. La seconde série de macrocycles est synthétisée via une glycosylation intramoléculaire, en utilisant dihydroxyazobenzène comme attache. Dans cette approche, l’efficacité et la stéréoselectivité de glycosylation sont étudiées en modulant la nature de liens et la configuration d’azobenzène. / As excellent photochromic molecules, azobenzene derivatives have increasing applications in the spatial and temporal photocontrol of molecular conformation, chemical reactivity, biological and pharmacological activities. In this context, an exciting attempt is introducing a photochromic motif into carbohydrate-containing macrocycles, a unique class of products with growing attention in medicinal and material science, so as to modulate their physicochemical, chemical and biologic properties by light.Two series of photoswitchable glycomacrocycles have been prepared in this thesis. The first one is obtained from 2,2’-dihydroxyazobenzene and di-O-bromoacetyl glycosides via one-pot O-alkylation approach. These macrocycles show excellent photophromic properties with high fatigue resistance. Chirality transfer from sugar to azobenzene moiety has been observed. One of the macrocycles can form organogel that responses to photo-, thermal- and mechanical stimulus. The second series of glycomacrocycles were prepared through intramolecular glycosylation by using dihydroxyazobenzene as tether. The efficiency and the stereoselective outcome of glycosylation have been investigated by modulating the nature of the linkers and the configuration of the azobenzene tether.
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Studies on the coordination chemistry of macrocyclic ligandsLippolis, Vito January 2000 (has links)
No description available.
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Synthesis and coordination chemistry of functionalised phosphazanesBenson, Callum Giles Maxwell January 2016 (has links)
This thesis focuses on the chemistry of novel phosphazane species derived from the chloro-phosphazanes [ClP(μ-NR)]$_2$ and their use as ligands and building blocks for macrocyclic compounds. The introduction (Chapter 1) surveys previous literature in the area, which is pertinent to the new studies. One of the most important issues is the various ways in which dimeric phosph(III)azanes can be employed as precursors for new ligands and in the design of new types of inorganic macrocycles. In Chapter 2 the synthesis of new chloro-dimers of the type [ClP(μ-NR)]$_2$ is described, which are the primary starting materials. Chapter 3 concerns the substitution at the chlorine atoms of [ClP(μ-NR)]$_2$ by LiSH to give a variety of sulfur-containing PV species [S=P(H)(μ-NR)]$_2$. The thermodynamic preference for the cis or trans isomers of the latter are explored by detailed NMR spectroscopic and DFT calculation investigations. Deprotonation of the $^t$Bu derivative [S=P(H)(μ-N$^t$Bu)]$_2$ using organometallic bases (Chapter 3) led to the isolation of s-block salts (Mg$^2+$, Na$^+$, K$^+$) of the P$^III$ dianion [S-P(μ-N$^t$Bu)]$^2_2-$. The Mg$^2+$ salt was found to form a mononuclear complex in the solid state whereas the Na$^+$ salt formed a large cage comprising eight dianions and 16 Na$^+$ ions built around a NaSH core. These s-block metal salts were shown to be useful transfer reagents for the dianion towards complexation with main group metals (e.g., Sn and Ge). Chapter 4 explores the oxidation of the P$^III$ dianions [S-P(μ-N$^t$Bu)]$^2_2-$ by chalcogens to give the more stable P$^V$ species [(E=)P$^V$(-S)(μ-N$^t$Bu)]$^2_2-$ (E = S, Se). The increase in stability and lower reducing ability of the P$^V$ dianion allowed the formation of complexes with transition and main group metals. Reaction of [(E=)PS(μ-N$^t$Bu)]$^2_2-$ with chloro-dimers [ClP(μ-NR)]$_2$ led to the formation of homo- and heteroleptic P$^III$-P$^V$ phosphazane macrocycles of the type [{S=PV(μ-N$^t$Bu)}2(u-E){P$^III$(μ-NR)}$_2$]. These can be oxidised to give air- and moisture-stable all-P$^V$ species [{S=P$^V$(μ-N$^t$Bu)}$_2$(μ-E){S=P$^V$(μ-NR)}$_2$] by reaction with elemental sulfur. Finally, in Chapter 5 the substitution of the chlorine atoms in [ClP(μ-NR$^1$)]$_2$ by amines (R$^2$NH$_2$) is explored, to give a range of bis(amino) cyclophosphazanes [(R$^2$NH)P(-NR$^1$)]$_2$ containing chiral and non-chiral R$^2$ and R$^1$ groups. These species were used in the formation of early transition metal (Zr, Ti, Hf) complexes which are potential pre-catalysts for alkene polymerisation studies.
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Studies towards synthetic receptors for small peptides and sugarsFlack, Stephen Sean January 1995 (has links)
No description available.
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