| dc.description.abstract | The main goal of this thesis was to explore and compare two protection strategies yielding 2,3,4-tri-O-benzyl-α-D-glucopyranosides. Further work was done to functionalize the primary 6- hydroxyl position to a sulfonic acid moiety yielding sulfoquinovose derivates 10a/b. Subordinate goals have been the optimization of the individual reactions for larger scale synthesis. Where possible, full spectroscopic characterization of intermediates, using appropriate NMR experiments was performed, enabling assignment of all relevant 13C and 1H shifts for most intermediates.
2,3,4-tri-O-benzyl-α-D-glucopyranoside intermediates 7a/b were reached in 42-55% yield through pathway 1, employing acetal protection of O-6 and O-4, with a following simultaneous protection of O-2 and O-3 as benzyl ethers before regioselective ring cleavage, leaving the free hydroxyl at the primary position. High anomeric control was achieved, with no observable β-anomer for the methyl glucosides 5-7a. After purification, and some optimization work, an anomeric ratio of 20:1 (α: β) was observed for allyl glucosides 5-7b. Separation of the anomers was not attempted.
Mono-protection of the primary alcohol with a triphenylmethyl group was deemed a less suited pathway due to low initial yields of 4a (54%) and unsuccessful purification and analysis of compounds 3b and 4b, attempting a wide array of purification techniques. The path was not explored further than intermediates 4a/b.
Further functionalization of the primary alcohol was performed by initial introduction of 4-toluenesulfonyl, yielding 8a/b in 80-87%. Thioacetates 9a/b (83-84%) were prepared using potassium thioacetate as a nucleophile. Oxidation of the thioacetates to the corresponding sulfoquinovose derivatives 10a/b (77-85%) was performed with potassium peroxymonosulfate, requiring some optimization of workup procedures. Novel reactions in the protection of the formed sulfonic acid moiety as silyl ethers were unsuccessful, indicating a need for exploring other possibilities for the protection of sulfoquinovose derivates 10a/b.
Effects of anomeric substituents were observed in the initial protection steps of the synthesis with the allyl glucosides, having yields 10-15% lower than that of the corresponding methyl glucopyranoses. In addition, differences in the oxidation of thioacetate 9a/b were observed, with several problematic aspects in purification and analysis of 10b.
Model substrates of tert-Butyldimethylsilyl(TBDMS)- and tert-butyldiphenylsilyl (TBPDS)- protected alcohols were procured. The substrates were subjected to the conditions employed in the oxidation of 9a/b in order to assess the compatibility of the overall protection strategy of the research project. Both silyl ethers were found to withstand the conditions. | |
