4-Oxoheptanedioic acid: an orthogonal linker for solid-phase synthesis of base-sensitive oligonucleotides

: Leisvuori A, Poijarvi-Virta P, Virta P, Lonnberg H

Publisher: PERGAMON-ELSEVIER SCIENCE LTD

: 2008

Tetrahedron Letters

TETRAHEDRON LETTERS

: TETRAHEDRON LETT

: 49

: 26

: 4119

: 4121

: 3

: 0040-4039

DOI: https://doi.org/10.1016/j.tetlet.2008.04.131

1,6-Dioxaspiro[4,4]nonane-2,7-dione has been found to react readily with alcohols in the presence of 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU). The 4-oxoheptanedioic acid tether obtained bears (1) a free carboxy group, which enables anchoring to aminoalkylated resins, and (2) a 4-oxobutanoate structural motif, which allows release of the target alcohol by a mild hydrazinium acetate treatment. To demonstrate the applicability of the procedure, nucleosides have been derivatized with this simple difunctional linker arm, anchored to a solid phase and subjected to synthesis and subsequent release of oligonucleotides bearing a base-sensitive biodegradable phosphate protection. (C) 2008 Elsevier Ltd. All rights reserved.

Chemical sciences