Exploration of steroselective cleavage of 4, 5-epoycholestane-3, 6-diols and stero controlled epoxidation of cholest-4-en-3 β, 6β-diol-6-acetate

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Covalent attachment of chiral manganese(III) salen complexes onto functionalised hexagonal mesoporous silica and application to the asymmetric epoxidation of alkenes

Two modified Jacobsen-type catalysts were anchored onto an amine functionalised hexagonal mesoporous silica (HMS) using two distinct anchoring procedures: (i) one was anchored directly through the carboxylic acid functionalised diimine bridge fragment of the complex (CAT1) and (ii) the other through the hydroxyl group on the aldehyde fragment of the complex (CAT2), mediated by cyanuric chloride. The new heterogeneous catalyst, as well as the precedent materials, were characterised by elemental analyses, DRIFT, UV-vis, porosimetry and XPS which showed that the complexes were successfully anchored onto the hexagonal mesoporous silica. These materials acted as active heterogeneous catalysts in the epoxidation of styrene, using m-CPBA as oxidant, and α-methylstyrene, using NaOCl as oxidant. Under the latter conditions they acted also as enantioselective heterogeneous catalysts. Furthermore, when compared to the reaction run in homogeneous phase under similar experimental conditions, an increase in asymmetric induction was observed for the heterogenised CAT1, while the opposite effect was observed for the heterogenised CAT2, despite of CAT2 being more enantioselective than CAT1 in homogeneous phase. These results indicate that the covalent attachment of the Jacobsen catalyst through the diimine bridge leads to improved enantiomeric excess (%ee), whereas covalent attachment through one of the aldehyde fragments results in a negative effect in the %ee. Using α-methylstyrene and NaOCl as oxidant, heterogeneous catalyst reuse led to no significant loss of catalytic activity and enantioselectivity. © 2005 Elsevier Inc. All rights reserved.

Asymmetric epoxidation of alkenes by a chiral manganese(III) salen complex anchored onto a functionalised hexagonal mesoporous silica

A Jacobsen-type catalyst was anchored onto an amine functionalised hexagonal mesoporous silica (HMS) through the diimine bridge fragment of the complex. The new heterogeneous catalyst, as well as the precedent materials, were characterised by elemental analyses, FTIR-DRIFT, UV-vis, porosimetry and XPS which showed that the complex was successfully anchored. This material was active in the epoxidation of styrene and α-methylstyrene in dichloromethane at 0°C using, respectively, m-CPBA/NMO and NaOCl. With the former substrate no asymmetric induction was found in the epoxide, whereas with the latter substrate higher %ee was found than in homogeneous phase. Using the latter experimental conditions, catalyst reuse led to no significant loss of catalytic activity and enantioselectivity. © 2005 Elsevier B.V. All rights reserved.

Enzyme catalysed modification of polymers

The aim of this project was to investigate the enzyme catalysed modification of synthetic polymers. It was found that an immobilised lipase from Candida antartica (Novozyme 435) catalysed the selective epoxidation of poly(butadiene) in the presence of hydrogen peroxide and catalytic quantities of acetic acid. The cis and trans double bonds of the backbone were epoxidised in yields of up to 60 % whilst the pendent vinyl groups were untouched. The effect of varying a number of reaction parameters was investigated. These studies suggested that higher yields of epoxide could not be obtained because of the conformational properties of the partially epoxidised polymer. Application of this process to the Baeyer-Villiger reaction of poly(vinyl phenyl ketone) and poly(vinyl methyl ketone) were unsuccessful. The lack of reactivity was found to be a property of the polymer rather than the enzymatic system employed. Attempts to modify hydroxyl containing polymers and polymers bearing active esters close to the polymer backbone were unsuccessful. Steric factors appear to be the most important influence on the outcome of the reactions.

Novel materials for membrane separation processes

The aim of this work was to synthesise a series of hydrophilic derivatives of cis-1,2-dihydroxy-3,5-cyclohexadiene (cis-DHCD) and copolymerise them with 2-hydroxyethyl methacrylate (HEMA), to produce a completely new range of hydrogel materials. It is theorised that hydrogels incorporating such derivatives of cis-DHCD will exhibit good strength and elasticity in addition to good water binding ability. The synthesis of derivatives was attempted by both enzymatic and chemical methods. Enzyme synthesis involved the transesterification of cis-DHCD with a number of trichloro and trifluoroethyl esters using the enzyme lipase porcine pancreas to catalyse the reaction in organic solvent. Cyclohexanol was used in initial studies to assess the viability of enzyme catalysed reactions. Chemical synthesis involved the epoxidation of a number of unsaturated carboxylic acids and the subsequent reaction of these epoxy acids with cis-DHCD in DCC/DMAP catalysed esterifications. The silylation of cis-DHCD using TBDCS and BSA was also studied. The rate of aromatisation of cis-DHCD at room temperature was studied in order to assess its stability and 1H NMR studies were also undertaken to determine the conformations adopted by derivatives of cis-DHCD. The copolymerisation of diepoxybutanoate, diepoxyundecanoate, dibutenoate and silyl protected derivatives of cis-DHCD with HEMA, to produce a new group of hydrogels was investigated. The EWC and mechanical properties of these hydrogels were measured and DSC was used to determine the amount of freezing and non-freezing water in the membranes. The effect on EWC of opening the epoxide rings of the comonomers was also investigated

Synthesis and cytotoxity of oxysterols:studies on the A,B ring polyoxygenated sterols

Oxysterols (OS), the polyoxygenated sterols, represent a class of potent regulatory molecules for important biological actions. Cytotoxicity of OS is one of the most important aspects in studies of OS bioactivities. However, studies, the structure-activity relationship (SAR) study in particular, have been hampered by the limited availability of structurally diverse OS in numbers and amounts. The aim of this project was to develop robust synthetic methods for the preparation of polyhydroxyl sterols, thereof, evaluate their cytotoxicity and establish structure-activity relationship. First, we found hydrophobicity of the side chain is essential for 7-HC's cytotoxicity, and a limited number of hydroxyl groups and a desired configuration on the A, B ring are required for a potent cytotoxicity of an OS, after syntheses and tests of a number of 7-HC's analogues against cancer cell lines. Then polyoxygenation of cholesterol A, B rings was explored. A preparative method for the synthesis of four diastereomerically pure cholest-4-en-3,6-diols was developed. Epoxidation on these cholest-4-en-3,6-diols showed that an allyl group exerts an auxiliary role in producing products with desired configuration in syntheses of the eight diastereomerically pure 45-epoxycholestane-3,6-diols. Reduction of the eight 45-epoxycholestane-3,6-diols produced all eight isomers of the cytotoxic 5α-acholestane 3β,5,6β-triol (CT) for the first time. Epoxide ring opening with protic or Lewis acids on the eight 45-epoxycholestane-3,6-diols are carefully studied. The results demonstrated a combination of an acid and a solvent affected the outcomes of a reaction dramatically. Acyl group participation and migration play an important role with numbers of substrates under certain conditions. All the eight 4,5-trans cholestane- 3,4,5,6-tetrols were synthesised through manipulation of acyl participation. Furthermore these reaction conditions were tested when a number of cholestane-3,4, 5,6,7-pentols and other C3-C7 oxygenated sterols were synthesised for the first time. Introduction of an oxygenated functional group through cholest-2-ene derivatives was studied. The elimination of 3-(4-toluenesulfonate) esters showed the interaction between the existing hydroxyls or acyls with the reaction centre often resulted in different products. The allyl oxidation, epoxidation and Epoxide ring opening reactions are investigated with these cholest-2-enes.