Alternative syntheses of (S)-cEt-BNA: a key constrained nucleoside component of bioactive antisense gapmer sequences.
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.
Department of Chemistry, Université de Montréal , Montréal, Québec H3C 3J7, Canada.
Juan C
JC
Salinas
Michael T
MT
Migawa
Bradley L
BL
Merner
Stephen
S
Hanessian
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis; D003500:Cyclization; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis; D013941:Thymine / Q000138:chemical synthesis* / Q000737:chemistry*; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry*
D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D004988:Ethers, Cyclic; D009705:Nucleosides; D016376:Oligonucleotides, Antisense; C005287:oxetane; D013941:Thymine; D014529:Uridine