title: Amide-Linked Ribonucleoside Dimers Derived from 5'-Amino-5'-deoxy- and 3'-(Carboxymethyl)-3'-deoxynucleoside Precursors(1).
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602-5700.
authors.forename: Matt A.
authors.initials: MA
authors.lastname: Peterson
authors.forename: Bradley L.
authors.initials: BL
authors.lastname: Nilsson
authors.forename: Sanchita
authors.initials: S
authors.lastname: Sarker
authors.forename: Bogdan
authors.initials: B
authors.lastname: Doboszewski
authors.forename: Weijian
authors.initials: W
authors.lastname: Zhang
authors.forename: Morris J.
authors.initials: MJ
authors.lastname: Robins