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This thesis describes the synthesis of some novel carbohydrate lactones and their uses as starting materials in (a) the syntheses of various polyfunctionalised cyclopentanes, via intramolecular aldol condensations, (b) the synthesis of 1-epihydantocidin, in which the crucial synthetic step involves a novel transformation induced by tetra-n-propylammonium perruthenate, and (c) the syntheses of various tetrahydrofurans and tetrahydropyrans. The syntheses of 3,4-O-isopropylidene and cyclohexylidene altrono and allono-1,5-lactones via Kiliani ascension of protected forms of D-ribose are described. The stereochemistry of the major reaction product, which was identified as 2,3-O-isopropylidene-D-altrono-l,5-lactone was confirmed by X-ray diffraction. Introduction of azide and iodide at C-2 is achieved via silyl protection of C-6 and formation of the 2-O-triflates. Nucleophilic displacement with azide or iodide produces mixtures of C-2 epimers. Desilylation is readily achieved by treatment with acetic acid to yield azido and iodo alcohols. Attempted oxidation of C-6 to an aldehyde functionality, in an attempt to effect cyclopentane formation via intramolecular aldol condensation of C-2 onto C-6 failed. Treatment of altrono and allono azido alcohols with tetrapropylammonium perruthenate unexpectedly results in the formation of a [2.2.2.] bicyclic hemiaminal, whose structure was confirmed by X-ray diffraction. Conversion of the amine functionality to a urea is effected by treatment with potassium cyanate. Cyclisation of the urea functionality onto the lactone carbonyl and subsequent deprotection effects the synthesis of 1-epihydantocidin. Investigations into acid catalysed epimerisation of the spiro centre in both hydantocidin and 1-epihydantocidin are described. Potassium carbonate induced ring contraction of 6-O-silyl altrono- and allono- 1,5-lactone-2-O-triflates yields tetrahydrofurans, the stereochemistry of which is confirmed by conversion to symmetric materials. Intramolecular Mitsunobu cyclisation of OH-2 onto C-6 of altrono-1,5-lactones effects tetrahydropyran formation. Inversion of C-5 of the known 3,4:5,6-di-O-ispropylidene-D-glycero-D-galacto-heptono- 1,5-lactone is described. Confirmation of product stereochemistry is achieved by conversion to 2,3-O-isopropylidene-L-altrono-1,5-lactone. Introduction of iodide and azide at C-2 is achieved via the formation of the 2-O-triflate. Selective deprotection of the 5,6 isopropylidene and subsequent periodate cleavage yields aldehydo lactones which undergo potassium fluoride induced intramolecular aldol cyclisation, to yield bicyclic [2.2.1.] azido and iodo carbocycles. Sodium azide induced intramolecular aldol cyclisation of 5-azido-5-deoxy-3,4-O-isopropylidene-L-galacturono-2,6-lactone, which produces two [2.2.1.] bicyclic azido carbocycles, is described. The second azido carbocycle, which is found to be the major reaction product, readily undergoes a retro aldol reaction, resulting in the formation of a third azido carbocycle, the structure of which was confirmed by X-ray diffraction. Investigations into the equilibration of these three bicyclic [2.2.1.] azido carbocycles under the reaction conditions employed to effect their formation are described. Various ring opening reactions of the second and third materials, and their uses in the syntheses of a novel amino pentol, two novel tetrahydroxy cyclopentane spirohydantoins and two novel cyclopentane amino acids are described. The structure of the asymmetric amino acid was confirmed by X-ray diffraction. Under basic reaction conditions retro aldol equilibration is seen to compete effectively with ring opening.

This thesis describes the syntheses of some polyfunctionalised cyclopentanes via intramolecular aldol condensations of sugar δ-lactone precursors. The known azido carbpcycle (1S,2R,3S,4R,5R)-methyl [5-azido-1,2,3,4- tetrahydrpxy-2,3-O-isopropylidene-cyclopentane] carboxylate was prepared from 2- deoxy-2-iodo-3,4:6,7-di-O-isopropylidene-D-glycero-D-talo-heptono-1,5-lactone in five steps. The key reaction was a base-induced intramolecular aldol cyclisation of a 5- iodo-formyl-2,6-lactone. Borohydride reduction of the methyl ester gave an azido triol. Deprotection followed by reduction of the azide functionality produced an amino pentol. The analogous tetrahydroxy β-amino acid was synthesised from the azido carbocycle in three steps. The inhibitory activity of the amino pentol against human liver glycosidases is reported. Two azido bicyclic lactones, (1R,4R,5R,6R,7R)-4-azido-5,6,7-trihydroxy-5,6-0- isopropylidene-2-oxa-bicyclo[2.2.1]heptan-3-one and (1S,4S,5R,6R,7R)-4-azido- 5,6,7-trmydroxy-5,6-O-isopropydilene-2-oxa-bicyclo[2.2.1]heptan-3-one, were prepared from 3,4:6,7-di-O<./em>-isopropylidene-D-glycero-D-talo-heptono-1,5-lactone in five steps. The (1R,4R,5R,6R,7<em.R)-compound was further elaborated to give an amino pentol via a series of borohydride reduction / deprotection / catalytic hydrogenation. A novel carbocyclic spirohydantoin was synthesised by two alternative routes. The second route also provided access to an N'-phenyl spirohydantoin. The inhibitory activities of the amino pentol and the spirohydantoin against human liver glycosidases are reported. The azido bicyclic lactone triol (1R,4S,5R,6R,7R)-4-azido-5,6,7-trihydroxy-2-oxabicyclo[ 2.2.1]heptan-3-one underwent reduction of the azide functionality with concomitant epimerisation to give the (5S)-epimeric amine. The structure of this material was confirmed by X-ray diffraction analysis of a crystalline derivative. Treatment of the azido triol with base under non-aqueous conditions resulted in a retroaldol reaction to give the (5S)-epimeric azide, the relative configuration of which was determined by single crystal X-ray analysis. A third ketal protected azido bicyclic lactone was prepared via a base-induced retro-aldol epimerisation. Five tetrahydroxycyclopentane α-amino acids, including a pair of enantiomers, were synthesised from the azido bicyclic lactones. The structures of two of the α-amino acids were established by X-ray crystallographic analysis, whilst the enantiomeric compounds were identified using circular dichroism spectrometry. The diketal protected (2R,3R,4R,5R)-tetrahydroxy-cyclopentane α-amino acid was incorporated into six oligopeptides. Peptide coupling at the C-terminus of the carbocyclic amino acid was carried out using two amino acid tert-butyl esters. Chain extension at the N-terminus was achieved by reaction with N-benzyloxycarbonyl protected amino acids in the presence of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride as the carbodiimide reagent. Complete deprotection of a tetrapeptide is described.

No description available.

Graduation date: 1966

Thesis (M.S.)--Rochester Institute of Technology, 2008. / Typescript. Includes bibliographical references (leaves 92-105).

Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains xiii, 395 p.; also includes graphics Includes bibliographical references (p. 383-395). Available online via OhioLINK's ETD Center