Applications of 5-exo-trig thiyl radical cyclizations for the synthesis of thiosugars.
The application of thiyl-radical-mediated 5-exo-trig cyclization reactions for the preparation of a series of C-linked 4-thiofuranoside sugars has been investigated. The cyclization reactions were found to proceed in high yield with complete regioselectivity and moderate to excellent diastereoselectivity for a number of benzyl-protected precursors. The diastereoselectivity of the radical cyclization was determined by a number of factors, primarily the stereochemistry at the C-2 position and the nature of the substituents attached to the olefin. The cyclization reactions proceed via transition-state intermediates that favor formation of the 1,2-trans products. For D-sugars, a chairlike transition state is proposed. For L-sugars, both chair- and boatlike transition states could be considered. Inversion of the stereochemistry at C-4 also induced a significant effect on the diastereoselectivity of the radical process. The synthetic route is general for both D- and L-sugars and offers a highly novel and efficient strategy for accessing C-linked 4-thiofuranosides. A fluorescently labeled thiosugar was prepared as a putative glycosidase inhibitor.
Trinity Biomedical Sciences Institute, Trinity College , 152-160 Pearse Street, Dublin 2, Ireland.
Aoife
A
Malone
Eoin M
EM
Scanlan
D003500:Cyclization; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D013237:Stereoisomerism; D054330:Thiosugars / Q000138:chemical synthesis* / Q000737:chemistry
D004791:Enzyme Inhibitors; D054330:Thiosugars; D006026:Glycoside Hydrolases