Amide-Linked Ribonucleoside Dimers Derived from S′-Amino-5′-deoxy- and 3′-(Carboxymethyl)-3′-deoxynucleoside Precursors

Article abstract of DOI:10.1021/jo9908647

Treatment of tert-butyldimethylsilyl (TBDMS) derivatives of 3′-keto(adenosine or uridine) with [(ethoxycarbonyl)methylene]triphenylphosphorane gave exocyclic alkenes that underwent stereo-selective hydrogenation to give 3′-deoxy-3′-[(ethoxycarbonyl)methyl](Ado or Urd) analogues. Saponification provided the 3′-(carboxymethyl)-3′-deoxy(Ado and Urd) derivatives 37 and 38. Treatment of 37 or 38 with DCC and 5′-amino-2′,3′-bis-O-TBDMS-5′-deoxynucleosides gave the amide-linked dimers (74-82%). Activation of 37 or 38 with 4-nitrophenol/DCC, and direct coupling of the 4-nitrophenyl esters with 5′-amino-5′-deoxy(Ado or Urd) in pyridine also produced amide dimers efficiently (65-70%). Analogous activation of a 5′-O-DMT-protected carboxylate, and its coupling 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′-(carboxymethyl)-3′,5′- dideoxyuridine intermediate with 5′-amino-5′-deoxynucleosides gave amide-linked dimers (72-78%) that can serve as masked (azide reduction) 5′-amino dimers for analogous synthesis of extended amide-linked oligomers.