ORGN 475 |
| Complex nucleoside antibiotics present synthetic challenges beyond those of simple sugars or nucleosides. In particular, formation of the N-glycosyl linkage requires a donor that possesses functionality and ring structure with more Lewis basic sites than those of a simple donor such as D-ribofuranose tetraacetate. We find that thioglycosides offer a versatile alternative to the Vorbruggen nucleoside synthesis because they are more stable than anomeric acetates, yet more susceptible to site-selective Lewis acid activation, and, in some cases, more accessible synthetically. Thus diisopropylidene-D-allofuranose (1) was elaborated by a short route to the bicyclic thioglycoside donor 2, and then glycosylation with silylated N-benzoyladenine led to the octosyl adenine 3, an inhibitor of cyclic-AMP phosphodiesterases. Alternatively, glycosylation with 2 and methyl N,O-bis(trimethylsilyl)uracil-5-carboxylate followed by deprotection gave octosyl acid A (4).
|
|
Total Synthesis of Complex Molecules
1:00 PM-5:20 PM, Wednesday, 29 March 2006 Georgia World Congress Center -- C301, Oral
Division of Organic Chemistry |
