An expeditious route to the synthesis of adenophostin A

✍ Scribed by Nicole C.R. van Straten; Gijsbert A. van der Marel; Jacques H. van Boom

• Publisher: Elsevier Science
• Year: 1997
• Tongue: French
• Weight: 851 KB
• Volume: 53
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(97)00307-4

✦ Synopsis

Glycosylation of 1,2-O-isopropylidene-5-O-tert-butyldiphenylsilyl-o~-D-ribofuranose (8) with ethyl 3,4,6-tri-O-acetyl-2-O-benzyl-l-thio-~/l~-D-glucopyranoside (7) under the agency of Niodosuccinimide and trifluoromethanesulfonic acid afforded Gt-linked dimer 10 in 95% yield. Acetylation of 13, obtained after hydrogenation of 10 followed by pivaloylation of ll (---> 12) and deacetonation, yielded penta-acetate 14. Vorbriiggen-type condensation of 14 with bis-trimethylsilyl 6-Nbenzoyladenine (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.

Vorbriiggen-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.