Synthesis of 2',3'',4''-trisphosphate-containing analogs of adenophostin A

Adenophostin A analog 4 was prepared via trimethylsilyl trifluoromethanesulfonate (TMSOTf)-assisted glycosylation of (S)-6-N-diphenylacetyl-9-(2-tert-butyldiphenylsilyloxy-1-hydroxyprop-3-yl)-adenine (11) with trichloroacetimidate donor 12 to give dimer 13. Protective group manipulations on 13 followed by phosphitylation with N,N-diisopropyl-bis-[2-(methylsulfonyl)ethyl] phosphoramidite (17) and in situ oxidation gave, after deprotection, (25)-9-{1-(alpha-D-glucopyranosyloxy 3,4-bisphosphate)-2-monophosphate-prop-3-yl}-adenine (4) Condensation of phosphoryloxymethyladenosine 25 with D-arabinitol derivative 21 under the agency of TMSOTf afforded methylene acetal 26. Protective group manipulations (--> 32), phosphorylation, and deprotection yielded 3'-O-(D-arabinitol-4-O-methylene 2,3-bisphosphate)-adenosine 2'-monophosphate (5), a methylene acetal-containing analog of adenophostin A. (C) 1997 Elsevier Science Ltd.