SYNTHESIS OF 2',3'',4''-TRISPHOSPHATE-CONTAINING ANALOGS OF ADENOPHOSTIN-A

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