An expeditious route to the synthesis of adenophostin A

Article abstract of DOI:10.1016/S0040-4020(97)00307-4

Glycosylation of 1,2-O-isopropylidene-5-O-tert-butyldiphenylsilyl-α-D-ribofuranose (8) with ethyl 3,4,6-tri-O-acetyl-2-O-1-thio-α/β-D-glucopyranoside (7) under the agency of N-iodosuccinimide and trifluoromethanesulfonic acid afforded α-linked dimer 10 in 95% yield. Acetylation of 13, obtained after hydrogenation of 10 followed by pivaloylation of 11 (→12) and deacetonation, yielded penta-acetate 14. Vorbruggen-type condensation of 14 with bis-trimethylsilyl 6-N-benzoyladenine (9) gave adenosyl glucoside 17. Deacetylation of 17 resulted in migration of the pivaloyl group from the 2'-OH to the 3'-OH of the glucosyl moiety (→18), giving access, after phosphorylation and deprotection, to adenophostin A analog 4 containing two (2'-4')-cis oriented phosphate groups. Vorbrugen-type condensation of 9 with 16, obtained by deacetonation of 10 and subsequent acetylation, gave adenosyl glucoside 22. Protective group manipulations followed by phosphorylation furnished, after deprotection, homogeneous adenophostin A (2) in a high overall yield.