The stereoselective synthesis of arabinofuranosides

Abstract

The work presented in this thesis is concerned with the design and development of chemical methods for the stereoselective synthesis of [beta]-L-arabinofuranosides, in particular those which constitute the oligosaccharide fragments of the plant glycoprotein extensin. Previous methods intended for the preparation of 1,2-cis-glycofuranosides are reviewed. Relevant mechanistic and conformational studies are also discussed. Selected glycosylation methods are examined in preliminary experiments with the model secondary alcohols - isopropanol and cholesterol. Of the methods investigated, the most successful proved to be that involving 2, 3, 5-tri-O-benzyl-a-L-arabino-furanosyl chloride and promoters consisting of silver or thallium cations supported on molecular sieves. Good yields (60-90[percent]) of the B-glycosides were obtained using stoichiometric amounts of reactants, in less than 4 hours at room temperature. The majority of these glycosylations proceeded with high (-9:1)B-stereoselectivity. However, with one promoter(based on thallium) a reversal of stereoselectivity was observed. The 1-0-trichloroacetimidate and 1-0-toluene-sulphonate derivatives of 2,3,5-tri-0-benzy1-L-arabinofuranose were also synthesised and studied as potential glycosylating agents. Four new derivatives of trans-4-hydroxy-L-proline have been synthesised, characterised, and used in glycosylation reactions with 2,3,5-tri-0-benzyl-arabinofuranosyl-oc-L-chloride and the molecular sieve-based promoters. The resulting B-arabino-furanosides were characterised, and each subsequently deblocked, to give the known component of extensin; 4-0-(B-L-arabinofuranosyl)-trans-oxy-L-proline.A number of other new derivatives were made and characterised during this work. These includeallyl-L-arabinofuranoside which provided an improved preparation of the known 2,3,5-tri-O-benzyl-L-arabinofuranose. An analogous synthesis of thecorresponding D-ribose derivative was also achieved. Throughout this work, extensive use has been made of and nmr spectroscopy in the identificationand characterisation of the new compounds. In particular, 13C nmr spectroscopy provided a veryconvenient means of establishing the ring sizes and anomeric configurations of the sugars.