Recovery, Purification, and Reusability of Building Blocks for Solid Phase Synthesis

Abstract

reagents and protecting group strategies, solid phase approaches regularly rely on the use of a high excess of building blocks and reagents in every addition step. Repetitive coupling of the same building block achieves full conversion; however, this comes at the cost of excess nonconjugated building blocks which end up in the waste. For example, for the standard Fmoc peptide synthesis of a decamer, amino acids are used in 5-10 equivalents (eq.) per coupling and double couplings are performed, resulting in 40-180 eq. of amino acids that will end up in the solvent waste. While many building blocks for the synthesis of peptides and oligonucleotides are commercially available at low cost, other building blocks are rare or commercially more expensive. Examples of such building blocks include non-natural amino acids, 13 C-and 15 N-labeled amino acids, and glycan donors. [5,[8][9][10][11][12] For building blocks that have to be synthesized prior to SPS, for example, glycosylated building blocks or building blocks that are used in the SPS of synthetic polymers, the use of excess building blocks is a major limitation in terms of cost, time, and labor. [13] Within the last decade, polymer chemists have successfully developed advanced strategies to introduce monomer sequence-control into synthetic polymers giving access to materials with new properties and applications such as drug delivery and data storage. [14][15][16][17] Indeed, several of these strategies rely on the use of solid phase synthesis and the assembly of tailor-made building blocks. [18] For example, Lutz et al. reported a SPS strategy for monodisperse and sequenceencoded poly(alkoxyamine amides) that allow for the storing of information in single polymer chains. [19,20] In the previous work, we have introduced the SPS of glycooligoamides as mimetics of oligosaccharides and their use in antibacterial treatment. [21,22] Although macromolecules synthesized via SPS can be expected to be high value products to enter the market in smaller quantities compared to commodity polymers, finding ways to produce such materials at low cost and with resource efficiency might further strengthen their applicability.Here we present the recovery, purification, and reusability of building blocks used in the solid phase assembly of glycooligoamides. The process relies on simple and well-established methods such as precipitation and recrystallization, and does not require any special equipment or expertise. It can be integrated into a standard peptide synthesizer for automated synthesis and is suitable for chemically different building blocks, as demonstrated here for tailor-made dimer building blocks, Solid phase synthesis (SPS) is well established for the synthesis of biomacro molecules such as peptides, oligonucelotides, and oligosaccharides, and today is also used for the synthesis of synthetic macromolecules and poly mers. The key feature of this approach is the stepwise assembly of building blocks on solid support, enabling monodispersity and monomer sequence control. Howe...

Detection of Lectin Clustering in Self‐Assembled, Glycan‐Functionalized Amphiphiles by Aggregation‐Induced Emission Luminophores

“…As building blocks, previously established TDS (triple‐bond diethylenetriamine coupled with succinic acid), [ 9 ] ADS (azide diethylenetriamine coupled succinic acid), HDM (hexamethylenediamine coupled with maleic acid) along with azido‐functionalized acetylated α ‐D‐Man, β ‐Gal, CATE (carboxylated aromatic thioether luminophore) and the commercially available functional TPE luminophores were used. [ 37–43 ]…”

“…As building blocks, previously established TDS (triple-bond diethylenetriamine coupled with succinic acid), [9] ADS (azide diethylenetriamine coupled succinic acid), HDM (hexamethylenediamine coupled with maleic acid) along with azido-functionalized acetylated 𝛼-D-Man, 𝛽-Gal, CATE (carboxylated aromatic thioether luminophore) and the commercially available functional TPE luminophores were used. [37][38][39][40][41][42][43] In short, the synthesis started from an amine-functionalized preloaded glycine resin and employed the stepwise addition of building blocks, which carry a free carboxylic acid group for attachment onto the resin and a protected amine group. Coupling was promoted by using the activation reagent benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate to form the active ester derivative.…”

Glycan-Presenting Coacervates Derived from Charged Poly(active esters): Preparation, Phase Behavior, and Lectin Capture

“…The oligomer scaffolds were prepared via solid phase assembly of tailor-made building blocks employing the Fmoc strategy using an automated peptide synthesizer (CSBio, USA), as established previously . Building blocks and carbohydrate azides were synthesized based on the literature, − Fmoc-Lys­(Boc)-OH and 1-ethynyl-4-(1,2,2-triphenylethenyl) benezene (TPE) dyes were acquired from BLD Pharmatech GmbH, Germany.…”

Expeditious Synthesis of a Glycopeptide Library

“…[26] As a result, the commercial availability of most GAAs is low, and the ones available are remarkably expensive. Second, while attempts at reagent recycling have been reported, [27] standard SPPS protocols rely on the use of high molar excess of amino acids to ensure reaction completion. [28] This sets a significant limit in GP synthesis considering the inaccessibility of GAAs.…”