Original Article:
Acyclic analogs of nucleosides based on tris(hydroxymethyl)phosphine oxide: synthesis and incorporation into short DNA oligomers
Barbara Nawrot, et al.
Heterocyclic Communications, 2015, 21. 303-314.
10.1515/hc-2015-0173
In this study, a series of novel DNA analogs were obtained by incorporating phosphinylidynetrimethanol (tris(hydroxymethyl)phosphine oxide, THPO)-derived residues (acyclic nucleoside analogs) into oligonucleotide chains. The resulting THPO-DNA analog showed reduced affinity for the complementary DNA strand and was resistant to snake venom and calf spleen exonuclease.
The specific synthetic steps can be divided into three parts, including: (1) Proper protection of THPO hydroxyl group; (2) THPO is functionalized by nucleobases and converted into phosphoramidite monomers; (3) Phosphoramidite derivatives of THPO-based acyclic nucleosides for automated solid-phase synthesis of chimeric DNA oligomers.
The diagram below shows the synthetic route for the conversion of tris(hydroxymethyl)phosphine oxide to acyclic nucleoside phosphoramidites. To selectively protect only one hydroxyl group, tris(hydroxymethyl)phosphine oxide 5 was treated with 1 molar equivalent of 4,4'-dimethoxytrityl chloride (DMT-Cl) in pyridine at room temperature. The second hydroxyl group in 6 was partially protected with tert-butyldimethylsilyl (TBDMS) after treatment with one molar equivalent of TBDMS-Cl (in the presence of a four-fold molar excess of imidazole).
Chemicals Related in the Paper:
| Catalog Number | Product Name | Structure | CAS Number | Price |
|---|---|---|---|---|
| ACM1067125 | Phosphinylidynetrimethanol |  |
1067-12-5 | Price |
