Synthesis of chemically and functionally diverse scaffolds from pentaerythritol

Abstract

Pentaerythritol(2,2-bis-hydroxymethyl-propane-1,3-diol) was converted into a series of mono-, di-, and trisubstituted derivatives, comprising ally1 ethers and amino-alkyl ethers, by systematic chemical manipulation of the hydroxy groups. The remaining hydroxymethyl group in the case of the trisubstituted analog was functionalized with ether groups bearing terminal o-carboxyl or o-alkene groups. These derivatives are versatile templates and scaffolds for single, double, or triple substitution with appropriate ligands forming amides and esters, and allowing the attachment of the w-alkene or o-carboxyl group to solid support for combinatorial chemistry.Key words: molecular diversity, scaffolds, templates and tris(2-aminoethy1)-pentaerythritol.RCsumC : Le pentaCrythritol(2,2-bis-hydroxymethyl-propane-1,3-diol) a CtC converti en une sCrie de dCrivCs mono-, di-et trisubstituis portant des groupes Cther allylique et Cther aminoalkyle par manipulation systkmatique des fonctions hydroxy. Le groupe hydroxymCthyle restant dans le cas des dCrivCs trisubstituks a CtC fonctionnalise par un des groupes ethers avec un groupe terminal carboxy ou alcinyle. Les derives sont utiles comme des sources de branchement des ligands pharmacologiquement actives par des liaisons amides ou ester. Des applications dans la chimie combinatorielle sur phase solide sont aussi envisageables.Mots elks : diversite moleculaire, tris(2-aminoethy1)-pentaerythritol.Recent interest in chemical diversity in conjunction with combinatorial methods of lead structure generation has instigated a search for readily available polyfunctional organic molecules that can be manipulated in a systematic manner (for recent reviews, see ref. 1). Such molecules can be utilized as templates or scaffolds onto which one can introduce variable functionality with spatially predetermined dispositions (2). For example, the incorporation of specific pharmacophores or related motifs at the extremities of such scaffolds can lead to binding at different receptor sites with potentially novel therapeutic applications (3). Alternatively, the attachment of the template or scaffold molecule to a polymer support through one of its arms, allows the voluntary elaboration of one or more remaining chains in a parallel or combinatorial mode for the discovery of biologically active sequences on growing chains. In the case of templates capable of replicating outwards from a core unit, it is possible to construct dendritic molecules (for selected examples, see ref. 4) with intriguing shapes and exciting physical properties.In connection with our interest in the general area of chemical and functional diversity (5), we wished to prepare organic templates capable of accommodating one, or more, bioactive molecules in order to release them in a sustained manner in a chemically or enzymatically induced process. Another objec- hanessia@ere.umontreal.ca tive was to prepare polyfunctional molecules that could allow us to generate clusters of immunologically relevant haptens on a given template...

Fast Access to Robust C‐Sialoside Multimers

“…This is illustrated by the efficacy of the cycloaddition between azide bearing C-sialoside 4 and tetrapropargyloxysilane, which furnished the tetravalent product 13 in 92 % yield (Scheme 2). The second approach to sialoclusters was also possible with the cycloaddition of alkyne C-sialoside 5 with various oligo-azide [23,24] core compounds. This approach is, however, potentially less attractive due to the hazardous manipulation of multi-azido compounds.…”

Improved Routes for the Preparation of Pentaerythritol Mono‐O‐benzyl Ether

“…Monosubstituted derivatives of pentaerythritol can be prepared directly in good yields [14,15] based on the reagent employed if 0.5 equiv or less of the reagent is used, particularly if the reagent employed is hindered, such as t-butyldimethylsilyl chloride. [14] Direct reaction with greater amounts of reagent leads to mixtures.…”

“…[14] Direct reaction with greater amounts of reagent leads to mixtures. [16] One general approach is available to monosubstituted derivatives.…”

Synthesis of clustered D-GalNAc (Tn) and D-Galβ(1→3)GalNAc (T) antigenic motifs using a pentaerythritol scaffold

“…In this paper, we report the synthesis of novel di-and trihaptenic clusters composed of Tn and T glycosides attached to linker arms derived from pentaerythritol (16). In the preceding paper (16) we described the synthesis of various podands prepared from pentaerythritol by suitable chemical modification.…”

“…In the preceding paper (16) we described the synthesis of various podands prepared from pentaerythritol by suitable chemical modification.…”