An Orthogonally Protected α,α-Bis(aminomethyl)-β-alanine Building Block for the Construction of Glycoconjugates on a Solid Support

Abstract

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. The assembly of the clusters involves removal of the amino protections of the solid-supported branching unit 1 in the order Fmoc, Boc, and Alloc, and subsequent coupling of peracetylated O-(glycopyranosyl)-N-Fmoc-L-serine pentafluorophenyl esters (galactose, glucose, mannose, and ribose) to each amino group exposed.

Click Multivalent Heterogeneous Neoglycoconjugates – Modular Synthesis and Evaluation of Their Binding Affinities

“…The reported hetero carbohydrate displays having a glycocluster,10,11 glycodendrimer,12–14 glycocyclodextrin,15 or glycopolymer16,17 architecture have been constructed by means of two different synthetic strategies for the incorporation of the different saccharide ligands: 1) by using an orthogonal protection of a polyfunctional core molecule for the successive attachment of the different sugar moieties10,11,13 or 2) by controlling the relative proportions of the carbohydrate reagents in the reaction with a homogeneous, functionalized, reactive core 12,14–17. In this last option, the heterogeneous functionalization can be performed following a sequential12,14,15 or a simultaneous16,17 conjugation pattern using pure carbohydrate reagents or mixtures of them, respectively, allowing in this way a modulation of the sugar density.…”

Solid‐Supported Synthesis of Bicyclic Peptides Containing Three Parallel Peptide Chains

“…[19] The second branching unit 2, used to cap the amino termini of the peptide chains, was synthesized as depicted in Scheme 1. Succinic acid monoallyl ester [20] and the di-tert-butyl ester of iminodiacetic acid [21] were condensed by HOAt/DCC [22] activation.…”

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

“…Heteromultivalent ligands, namely heteroglycoclusters (hGCs), represent ideal structures to achieve this purpose [5]. A few recent reports described the construction of various hGCs based on the successive attachment of sugar residues on a core scaffold such as sugar [6–7], peptide [8–10], dendrimer [11–12], cyclodextrin [13–15] and polymer [16]. The most common synthetic strategy to build such hGCs relies on a fragment-coupling approach using thiol–ene coupling [17], copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) [18] or S N 2 reaction [19].…”