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Title: Sugar lactones in synthesis
Author: Fairbanks, Antony J.
ISNI:       0000 0001 2408 9327
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 1993
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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.
Supervisor: Fleet, G. W. H. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Carbohydrates ; Synthesis ; Lactones Chemistry, Organic