Benzaldehyde Lyase-catalyzed intramolecular benzoin reactions

Abstract

Intramolecular stereoselective carboligations are important reactions in organic synthetic chemistry essential for the access of natural occurring compounds and analogues. Besides the chemical methodologies, a plethora of intramolecular C-C bond forming reactions exists in different metabolic pathways of living organism catalyzed by highly evolved enzymes. Examples of carboligases such as of aldolases or ThDP depending enzymes performing asymmetric intramolecular aldol reactions with synthetic substrates are scarce in the literature. In this work, we endeavored to investigate on the intramolecular C-C bond formation via benzoin reaction catalyzed by benzaldehyde lyase from Pseudomonas fluorescens biovar I (BAL). We investigate BAL-catalyzed intramolecular benzoin reaction on benzaldehyde moieties substrates connected with a spacer derivative via ether linkage (i.e. 2,2'- (1), 3,3’ (2) and 4,4’ (3)-(n-alkane-1,n-diylbis(oxy))dibenzaldehyde derivatives). The reaction performance comparing the intra and inter benzoin reaction with substrates 1-3 as well as their analogues with symmetric and unsymmetrical aromatic substitutions was investigated. The results obtained of substrate conversion, stereochemical outcome of the enzymatic reactions and molecular models that intended to explain the reactivity of the different substrates will be reported.