Doctoral Degrees (Chemistry and Polymer Science)

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Browsing Doctoral Degrees (Chemistry and Polymer Science) by Author "Ackerman, Louis Gabriel Jozua"

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    Structure elucidation of and synthetic approaches to monatin, a metabolite from Schlerochiton ilicifolius
    (Stellenbosch : Stellenbosch University, 1990-12) Ackerman, Louis Gabriel Jozua; Vleggaar, R.; Stellenbosch University. Faculty of Science. Dept. of Chemistry & Polymer Science.
    ENGLISH ABSTRACT: Monatin, or 4-hydroxy-4-(3-indolylmethyl) glutamic acid is a high-intensity sweet tasting amino acid found in the root bark of the indigenous plant Schlerochiton ilicifolius. In the thesis the isolation, structure elucidation and a number of synthetic approaches toward the total synthesis of monatin are described. Extensive fractionation of an aqueous extract of the root bark of S. ilicifolius using AG50WX8 strong acid cation exchange resin followed by successive gel filtration procedures using Biogel P2- and Sephadex G10 gels and guided by the intense sweet taste resulted in the isolation of monatin as a mixture of salts in which the sodium salt predominates. Potassium and calcium are the two other cations present. The structure elucidation is based mainly on the analysis of data obtained for monatin and the lactone ester of the N-2,4-dinitrophenyl derivative, prepared by reaction of monatin with Sangers reagent and diazomethane, by 1H and 13C n.m.r. techniques. The X-ray crystallographic study of both monatin and the derivative proved disappointing in that the reflections measured were weak and as a consequence refinement of the data was severely curtailed. However the resultant structures do show the skeletal atoms of the two compounds and in each case the relative stereochemistry of the two chiral centres could be deduced. A comparison of the specific rotation of monatin with those of related 4-hydroxy-4-methylglutamic acids indicates that monatin could have the (2S,4S) configuration. Retrosynthetic analysis of the monatin molecule identified a number of routes which could be utilized for the synthesis of monatin and analogues in which the indole moiety is replaced by a phenyl or aryl group. Seven approaches toward the synthesis of monatin were investigated using in most instances model compounds to establish optimum reaction conditions. Only the last approach, based on a 1,3-dipolar cyclo-addition reaction met with a measure of success: reaction of the 1,3-dipolar compound formed by reaction of N-t-Boc-indole-3-aldehyde with methyl N-benzylglycinate, with the dipolarophile methyl 2-acetoxyacrylate, generated a pyrrolidine with the requisite substituents needed for the monatin structure. In the event the final step, the cleavage of the C-2--N bond of the substituted pyrrolidine ring to give monatin, failed. During the investigation of the 1,3-dipolar cycloaddition reaction several substituted pyrrolidines were prepared. In each case several racemic stereoisomers were formed. In addition a number of substituted oxazolines and pyrrolizidines were obtained as minor by-products during these reactions. The stereochemistry of these compounds was deduced from the proton-proton nuclear Overhauser effect studies and X-ray crystallographic data.