Abstract
Approaches to the synthesis of the constrained 5-methyluracil nucleoside (S)-cEt-BNA, a key "gapmer" unit in a number of biologically relevant antisense oligonucleotides, are described using 5-methyluridine as starting material. In the shorter synthesis, a nine-step linear sequence afforded a O-protected (S)-cEt-BNA consisting of a [2.2.1]dioxabicycloheptane core in 7% overall yield. A competing reaction in an intramolecular cyclization of a tosylate led to a bicyclic oxetane.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Bridged Bicyclo Compounds / chemical synthesis*
-
Bridged Bicyclo Compounds / chemistry*
-
Bridged-Ring Compounds / chemical synthesis
-
Cyclization
-
Ethers, Cyclic / chemical synthesis*
-
Ethers, Cyclic / chemistry*
-
Molecular Structure
-
Nucleosides / chemical synthesis
-
Oligonucleotides, Antisense / chemical synthesis
-
Thymine / chemical synthesis*
-
Thymine / chemistry*
-
Uridine / analogs & derivatives*
-
Uridine / chemistry*
Substances
-
Bridged Bicyclo Compounds
-
Bridged-Ring Compounds
-
Ethers, Cyclic
-
Nucleosides
-
Oligonucleotides, Antisense
-
oxetane
-
Thymine
-
Uridine