A Re‐evaluation of the Use of Rink, BAL, and PAL Resins and Linkers

Abstract

The preparation of amine and guanidine derivatives of phenylalaninamide and tryptophanamide as well as benzylamines from BAL, Rink‐MBHA, and Rink resins has been performed. Cleavage of the target compound gave significant amounts of byproducts compounds in which the linker moiety was attached to the target unit. This side reaction can be avoided when the solid supports are prepared by anchoring the corresponding linker to an aminomethyl resin.

Solid-Phase Preparation of a Library Based on a Phenylalanine Scaffold

“…When the amine was transformed into a secondary amine by reductive amination, two products were obtained: the desired product 11, with purity percents (calculated by HPLC at 210 nm) ranging from 11 to 40, and the desired product incorporating the linker 12, with percents between 14 and 51 (Scheme 9). As described in the literature [16], this side reaction occurs under TFA/DCM (1 : 4) resin cleavage conditions. This unexpected cleavage occurred for substrates containing a basic center close to the linker.…”

Methods for the Peptide Synthesis and Analysis

“…Linkage to the solid support should be totally stable to all synthetic processes, including the final treatment that will detach the target compound from the solid support. Sometimes this bond is not totally stable and the carbocation-containing linker is detached from the solid support, causing further heterogeneity of the crude peptide or causing back-alkylation of the target compound [32,33]. This is the case of linkers attached to p-methylbenzhydrylamine (MBHA) resin when using a tert-butyloxycarbonyl (Boc) (13)/benzyl (Bzl) (20) strategy for preparing peptide amides.…”

“…This is the case of linkers attached to p-methylbenzhydrylamine (MBHA) resin when using a tert-butyloxycarbonyl (Boc) (13)/benzyl (Bzl) (20) strategy for preparing peptide amides. To overcome this side reaction, the use of aminobenzyl PS or aminoalkyl resins, which form a more acid-stable bond, is recommended [33]. Similar problems arise with (poly)alkoxybenzyl [34] (Wang (8), backbone amide linker (BAL), Rink (11))-type resins.…”

“…This reaction is irreversible and consumes the starting acid without generating peptide. A copious precipitate of N,N ′ -dicyclohexylurea separates within a few minutes in any reaction using N,N ′ -dicyclohexylcarbodiimide (33), which poses a problem in solid-phase synthesis because it cannot be removed by filtration. This has led to its replacement by N,N ′ -diisopropylcarbodiimide (DIC, 39), or N-ethyl-N ′ -(3-dimethylaminopropyl)carbodimide (EDC, 40), which gives an urea that is soluble in organic solvents.…”

Quinone-based fluorophores for imaging biological processes

“…5 Driven by the continued interest in the preparation of such sophisticated probes, considerable advances in overcoming the inherent difficulties in their synthesis have been attained. Such achievements have been possible with the design of novel and effective synthetic strategies that had been traditionally limited to medicinal chemistry research programmes, 6,7 such as multicomponent reactions, C-H activation processes and cycloadditions, among others. 8 While the chemistry of quinones and most aspects related to their synthesis, properties and usage have been surveyed in several review articles over the last decade, to date there were no reports covering the integration of quinones within fluorescent probes and their application for bioimaging studies.…”