Synthesis of 5′-C- and 2′-O-(Bromoalkyl)-Substituted Ribonucleoside Phosphoramidites for the Post-synthetic Functionalization of Oligonucleotides on Solid Support
✍ Scribed by Xiaolin Wu; Stefan Pitsch
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- German
- Weight
- 382 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0018-019X
No coin nor oath required. For personal study only.
✦ Synopsis
Dedicated to Prof. Dr. Frank Seela on the occasion of his 60th birthday
The preparation of building blocks for the incorporation of 6'-O-(5-bromopentyl)-substituted b-dallofuranosylnucleosides and 2'-O-[(3-bromopropoxy)methyl]-substituted ribonucleosides into oligonucleotide sequences is presented (Schemes 1 and 2). These reactive building blocks can be modified with a variety of soft nucleophiles while the (fully protected) sequence is still attached to the solid support. As an example of this strategy, we carried out some preliminary solid-phase substitution and conjugation reactions with DNA sequences containing a 2'-O-[(3-bromopropoxy)methyl]-substituted ribonucleoside (Scheme 3) and determined the pairing properties of duplexes obtained therefrom.
1 ) The connection of the nucleobase was determined by 13 C-NMR spectroscopy according to [8].
2 ) The correct position of the tom group was determined by 1 H-NMR spectroscopy according to [5].
Generally, within every pair of 5'-O-dimethoxytritylated, base-protected nucleosides with 2',3'-O-formaldehyde acetal-derived substituents known so far, we observed the following relationships: the 2'-Oalkylated nucleosides are less polar and elute faster on chromatography (silica gel) than the corresponding 3'-O-alkylated regioisomers; the HÀC(1') signals of the former are further downfield, and the coupling constants between HÀC(1')/HÀC(2') are smaller than the corresponding values of the latter.