posted on 1999-10-08, 00:00authored byMatt A. Peterson, Bradley L. Nilsson, Sanchita Sarker, Bogdan Doboszewski, Weijian Zhang, Morris J. Robins
Treatment of tert-butyldimethylsilyl (TBDMS) derivatives of 3‘-keto(adenosine or uridine) with
[(ethoxycarbonyl)methylene]triphenylphosphorane gave exocyclic alkenes that underwent stereoselective 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.