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dc.contributor.authorAli, Saiyad Asad Maqsooden
dc.date.accessioned2018-01-31T11:23:22Z
dc.date.available2018-01-31T11:23:22Z
dc.date.issued1968en
dc.identifier.urihttp://hdl.handle.net/1842/26790
dc.description.abstracten
dc.description.abstractThe structural relationship of cholesterol and bile acids was established on a chemical basis as early as the beginning of the 20th Century by Windaus. (For a review see "Steroids" by Fieser and Fieser.) but the first direct evidence that cholesterol was a biological precursor of bile acids was reported in 1943 (Bloch et.al J.Biol.Cliem. 149, 511). Since then, many studies on the degradation of cholesterol to bile acids have been made. These studies require postulated synthesized intermediates for biological testing, therefore the chemical synthesis of hypothetical intermediates is important. The main pathway for the biogenesis of cholic acid possibly involves initial hydroxylation of cholesterol at the 7α-position, followed by oxidation of the 3ß-hydroxyl group to give cholest-4-en-3-one-7α-ol. The 12α-hydroxyl group is probably then inserted and the molecule then reduced to the 5ß-cholestan-3α,7α,12α-triol. This is followed by co-oxidation of the side chain and then ß-oxidation and cleavage to cholic acid. The subject has been reviewed in this worken
dc.description.abstractThe aim of the present work was to produce a series of cholesterol derivatives which may be intermediates in cholesterol metabolism in living cells. In certain cases newer methods for the synthesis of known sterols were evolved. Methods for the improved separation of certain sterols had also to be worked out, and modern methods for criteria of purity were examined.en
dc.description.abstractThe 7α-hydroxy derivatives of cholesterol, 12α-, 24, 25 and II <J6-bydroxycholesterols - the triols, were prepared through the respective 7α-hydroperoxides by means of photosensitized oxygenations. Studies with the cholesterol-4-C¹⁴ revealed that with either very dilute solutions or concentrated solutions, the attack of molecular oxygen was not as highly specific as often stated. The stereospecificity of the mode of attack of molecular oxygen has been reviewed. The isolation of cholest-4-en-3ß,6ß-diol in photosensitized oxygenation of cholesterol is reported and its mode of formation discussed.en
dc.description.abstractIt is known that the 12α-hydroxylation reaction does not occur after either the 26-hydroxylation has been effected or the side chain oxidised to a C₂₄-acid. Certain novel compounds such as cholest-5-en-3ß,7α,24Σ-triol and cholest-5- en-3ß,7α,25-triol, are in the course of tritiation and the in vitro studies will be of interest to ascertain whether they are converted into cholic acid.en
dc.description.abstractThe substance 7ß-hydroxycholesterol was prepared by the NaBH₄ reduction of 7-ketocholesterol. Separation of the 7α and 7ß-epimers was achieved by chromatography of the diacetate as well as the free diols on neutral alumina. For successful separation of the free diols the amount of water in the alumina was critical. No separation was possible when no water was used, while the best separation was obtained with 1% water in the support.en
dc.description.abstractThe sterol, 12α-hydrocholesterol was prepared by a modified method of Danielsson (1963b)en
dc.description.abstractDeoxycholic acid was coupled with isovaleric acid, and 5ß-cholestan-3α,12α-diol thus obtained was oxidised to the 3-oxo compound by an Oppenauer method. The 4,5—double bond was introduced using SeO₂ in ethanol and cholest-4—en—3—one-12α-ol obtained in good yields. The reported method of Danielsson involved a 3-stage synthesis for the introduction of a 4,5-double bond, and the yields were low. The reduction of the enol-acetate of the oc,/3-unsaturated ketone with NaBH₄ gave the desired product. The working up procedure was also modified, and a new compound cholest-3,5-diene-12α-ol was isolated and identified as a side producten
dc.description.abstractAnother new compound i.e. 5ß-cholestan-3α,12α-diol-24-one was prepared by utilizing the known reaction of an acid chloride and di-isopropyl-cadmium. This compound could be used to prepare cholest-5-en-3ß,12α,24Σ-triol using the sequence of reaction described previously. Another interesting biological compound, cholest-5-en-3ß,7α,12α,24Σ-tetrol, can be obtained from this triol on photo-oxygenation and reduction as described in this work.en
dc.description.abstractThe 4ß, 22Σ, 24, 25, 26—hydroxycholesterols were prepared by modifications of the reported methods and 26-hydrocholesterol was prepared by two different routes. An impurity separated from 25-keto-nor-cholesterol acetate was identified as 3ß-acetoxy-20-hydroxy-5-cholenic acid lactone.en
dc.description.abstractCholestun-3ß,5α,6ß-triol, cholestan-3ß,5α-diol-6-one, 5α,6α-epoxycholesterol, cholest-6-en-3ß,5α-diol and cholestan- 3ß,5α-diol were prepared essentially by known methods.en
dc.description.abstractCholest-4-en-3-one-7α-ol was prepared by a known sequence but modification was made in the preparation of cholest-4,6- diene-3-one by the use of chloranil in the dehydrogenation of cholest-4-en-3-one.en
dc.description.abstractA number of intermediates involved in the inversion of the configuration at C₃ and the saturation of the double bond were synthesized. The starting materials for these compounds were saturated coprostanes, which were prepared by electrolytic coupling of the respective bile acids and isovaleric acid.en
dc.description.abstractHowever, there are still gaps in our knowledge of complete sequence of the degradation of cholesterol to the bile acids. A comprehensive understanding of the subject will only be possible when all the relevent hypothetical intermediates have been synthesized and are available for biological experiments.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2017 Block 15en
dc.relation.isreferencedbyAlready catalogueden
dc.titleSyntheses of possible steroid intermediates in bile acid biosynthesisen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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