Controlling and Measuring the Equilibration of Dynamic Combinatorial Libraries of Imines

Abstract

Imine formation is one of the most powerful methods for the construction of azamacrocycles, especially when combined with Dynamic Combinatorial Chemistry. Careful NaBH 4 reduction of the imine libraries opens the possibility of determination of their composition via HPLC analysis of the resulting amine mixture. Templates, reagent concentrations, as well as reaction conditions influence the library composition.

Dynamic combinatorial libraries of macrocycles derived from phthalic aldehydes and α,ω-diamines

“…Since no other method than mass spectrometry allow for resolution of imine mixtures, 26 the parent imine libraries were 'frozen' by reducing them with NaBH 4 according to the previously reported protocol 27 that, for furan-based imines, allowed for full conversion in less than 1 min. To simplify the isolation and purification of the obtained products, the resulting secondary libraries of macrocyclic amines were then converted into methyl carbamates (Scheme 4).…”

“…The reduction step was found to take less than 1 min, as performed and measured using previously presented UV-methodology. 27 Kinetic measurements were undertaken for all aldehyde (1, 2)damine (AeC) pairs showing rapid conversion of imines to amines in all the cases and thus ensuring that the original ratios of macrocyclic compounds were maintained. For evaluation of the carbamate protection step, the reaction of 2 with B was chosen.…”

Dynamic Combinatorial Chemistry: An Introduction

“…For example, Wessjohann and coworkers have demonstrated that Ugi reactions can efficiently halt equilibration of an imine DCL, combining an irreversible diversification process with a reversible library selection [ 24 ]. Xu and Giuseppone have integrated reversible imine formation with a self -duplication process [ 25 ], and Ziach and Jurczak have examined the ability of ions to template the synthesis of complex azamacrocycles [ 26 ]. The mechanistically related reactions of hydrazone [ 27 ] and oxime [ 28 ] exchange have also been explored as suitable foundations for DCL experiments.…”

Simple synthesis of a new family of 22- to 28-membered macrocycles containing two chalcone moieties

“…[18][19][20] Synthesis of other structurally related compounds and their suitable transformations to useful hosts are also reported. 21,22 Furthermore, very recently several types of macrocycles containing fused heterocyclic or homocyclic moieties have been synthesized [23][24][25][26][27][28][29] and a good number of them have shown some very interesting properties. It was therefore our endeavour to develop a simple synthesis of macrocycles containing more than one chalcone moiety.…”