Amide-linked ribonucleoside dimers derived from 5 '-amino-5 '-deoxy- and 3'-(carboxymethyl)-3 '-deoxynucleoside precursors

Treatment of tert-butyldimethylsilyl (TBDMS) derivatives of 3'-keto(adenosi ne or uridine) with [(ethoxycarbonyl)methylene]triphenylphosphorane gave ex ocyclic alkenes that underwent stereoselective hydrogenation to give 3'-deo xy-3'-[(ethoxycarbonyl)methyl](Ado or Urd) analogues. Saponification provid ed the 3'-(carboxymethyl)-3'-deoxy(Ado and Urd) derivatives 37 and 38. Trea tment of 37 or 38 with DCC and 5'-amino-2',3'-bis-O-TBDMS-5'-deoxynucleosid es gave the amide-linked dimers (74-82%). Activation of 37 or 38 with 4-nit rophenol/DCC, and direct coupling of the 4-nitrophenyl esters with 5'-amino -5'-deoxy(Ado or Urd) in pyridine also produced amide dimers efficiently (6 5-70%). Analogous activation of a 5'-O-DMT-protected carboxylate, and its c oupling with 5'-amino-5'-deoxy-2'-O-methyladenosine gave the amide dimer in good yield (74%). Coupling (DCC) of a 5'-azido-2'-O-TBDMS-3'-(carboxymethy l)-3', 5'-dideoxyuridine intermediate with 5'-amino-5'-deoxynucleosides gav e amide-linked dimers (72-78%) that can serve as masked (azide reduction) 5 '-amino dimers for analogous synthesis of extended amide-linked oligomers.