Radical-mediated bromination of peracetylated 5-thio-D-xylopyranosyl bromides: An easy access to the corresponding anomeric orthothiolactones

Article abstract of DOI:10.1016/0008-6215(95)00378-9

On treatment with N-bromosuccinimide in refluxing carbon tetrachloride under irradiation with visible light, both α and β anomers of 2,3,4-tri-O-acetyl-5-thio-D-xylopyranosyl bromide were converted mainly to 2,3,4-tri-O-acetyl-5-thio-D-xylopyranosylidene dibromide (5) and to 2,3,4-tri-O-acetyl-5(S)-5-bromo-5-thio-D-xylopyranosylidene dibromide (6). Whereas the more reactive β anomer could be transformed cleanly into the dibromide 5 after heating for 2 h, complete conversion of the α-bromide required a prolonged treatment (~ 5 h) leading to a mixture of di-, tri- and tetra-bromides. Similarly, an anomeric mixture of 2,3,4,6-tetra-O-acetyl-5-thio-D-glucopyranosyl bromide yielded mainly tribromide 11 after prolonged heating. The reaction rates and the structure of the products showed again the higher reactivity of axial C-H bonds at either C-1 or C-5 in pyranosyl rings towards S(H)2 processes. However, activation by the sulfur atom allowed attack of equatorial bonds as well and polybromination at both C-1 and C-5. Treatment of the C-1 dibromide 5 by silver triflate in the presence of either alcohols or thiols yielded the corresponding 5-thiosugar ortholactones 12-15. Methyl 1-methoxy-5-thio-D-xylopyranoside (18), obtained from 12 on deacetylation, showed no venous antithrombotic activity in rats according to a Wessler test.