An aminooxy-functionalized non-nucleosidic phosphoramidite for the construction of multiantennary oligonucleotide glycoconjugates on a solid support.

In this unit, a method is described that allows construction of multiantennary oligonucleotide glycoconjugates on a solid support. A bis(hydroxymethyl)malondiamide-based phosphoramidite that contains two phthaloyl-protected aminooxy groups compatible with normal chain assembly is prepared. The aminooxy functions can be deblocked with a hydrazinium acetate treatment and subsequently oximated on-support with fully acetylated 4-oxobutyl alpha-D-mannopyranoside.

Solid-phase synthesis of oligonucleotide glycoconjugates bearing three different glycosyl groups: orthogonally protected bis(hydroxymethyl)-N,N'-bis(3-hydroxypropyl)malondiamide phosphoramidite as key building block.

Diethyl O,O'-(methoxymethylene)bis(hydroxymethyl)malonate (3) was observed to undergo a stepwise aminolysis when treated with 3-aminopropanol. This allowed convenient preparation of bis(hydroxymethyl)-N,N'-bis(3-hydroxypropyl)malondiamide bearing orthogonal levulinyl (Lev) and tert-butyldiphenylsilyl (TBDPS) protections at the two N-hydroxypropyl groups (8). One of the hydroxylmethyl functions was then protected with a 4,4'-dimethoxytrityl (DMTr) group, and the other one was phosphitylated to obtain a methyl N,N-diisopropylphosphoramidite (1).

Solid-phase synthesis of multiantennary oligonucleotide glycoconjugates utilizing on-support oximation.

A novel method for preparation of multivalent oligonucleotide glycoconjugates on a solid support has been described. A pentaerythritol-based phosphoramidite (1) bearing two masked aminooxy groups has been used as the key building block. After conventional chain assembly, the aminooxy functions have been deblocked by a hydrazinium acetate treatment and subsequently oximated with fully acetylated 4-oxobutyl alpha-D-mannopyranoside.

An Orthogonally Protected alpha,alpha-bis(aminomethyl)-beta-alanine building block for the construction of glycoconjugates on a solid support.

Synthetic glycoclusters are extensively used as mimetics of naturally occurring, multivalent carbohydrate ligands in various glycobiological applications. Their preparation, however, is far from trivial, and it still is a limiting factor in the study of carbohydrate binding. We herein report the synthesis of an orthogonally protected building block, N-Alloc-N'-Boc-N' '-Fmoc-alpha,alpha-bis(aminomethyl)-beta-alanine (1), and its use in the preparation of triantennary peptide glycoclusters (21-24) on a solid support.