Tubulin-guided dynamic combinatorial library of thiocolchicine-podophyllotoxin conjugates

The use of tubulin as a target to influence the composition of the mixture from a dynamic combinatorial library, based on the disulfide bond exchange reaction, is described. ESI-FT-ICR-MS was used to determine the composition of the library. The heterodimeric compound amplified by this approach was used to design the homologous derivative with a two-carbon spacer in place of the disulfide function. The ability of the compounds to inhibit tubulin polymerization is reported and compared to thiocolchicine.     

Dithioacetal Exchange: A New Reversible Reaction for Dynamic Combinatorial Chemistry

Reversibility of dithioacetal bond formation is reported under acidic mild conditions. Its utility for dynamic combinatorial chemistry was explored by combining it with orthogonal disulfide exchange. In such a setup, thiols are positioned at the intersection of both chemistries, constituting a connecting node between temporally separated networks.     

Chiral ytterbium complex-catalyzed direct asymmetric aldol-Tishchenko reaction: synthesis of anti-1,3-diols

The asymmetric aldol-Tishchenko reaction of aromatic aldehydes with aliphatic and aromatic ketones has been developed as an efficient strategy for the synthesis of anti-1,3-diols in good yield with high diastereocontrol and good levels of enantioselectivity. This domino-type reaction is catalyzed by a chiral ytterbium complex that promotes both the aldol reaction through enolization of the carbonyl compound and the Evans-Tishchenko reduction of the aldol intermediate. The stereochemistry of the resulting diols is also investigated and finally proved by using CD techniques.     

Generation of a dynamic combinatorial library using sialic acid aldolase and in situ screening against wheat germ agglutinin

This paper describes the generation of a dynamic combinatorial library of sialic acid analogues using sialic acid aldolase. Addition of wheat germ agglutinin to the equilibrating libraries results in selective amplification of one or more members.     

Target-induced selection of ligands from a dynamic combinatorial library of mono- and bi-conjugated oligonucleotides

A dynamic library of 15 mono- and bi-conjugated oligonucleotides was generated from a pool of three aldehydes and an oligonucleotide bearing two reactive amino groups. Addition of complementary target to the equilibrating mixture of imines resulted in selective amplification of one conjugate. UV-melting experiments confirmed that it was the best ligand among those that were tested. This study emphasizes that dynamic combinatorial chemistry can be used to simultaneously identify the type and the location of appended residues for stabilizing oligonucleotide complexes.     

Protonic and temperature modulation of constituent expression by component selection in a dynamic combinatorial library of imines

The constitutional recomposition of a dynamic library of imines displays a complex behavior under the effect of two parameters, acidity and temperature. A qualitative analysis of the quantitative data is presented. The results illustrate the response of such a dynamic system to a physical stimulus (temperature) and a chemical effector (H+), thus demonstrating its adaptive behavior under the pressure of external factors. They also point to the possibility of modulating a given functional property (optical, electronic, ionic) by constitutional recomposition induced by a specific trigger. Such features are of great interest for the development of stimuli-responsive, functional dynamic materials.     

Amplification of bifunctional ligands for calmodulin from a dynamic combinatorial library

A well known strategy to prepare high affinity ligands for a biological receptor is to link together low affinity ligands. DCC (dynamic combinatorial chemistry) was used to select bifunctional protein ligands with high affinity relative to the corresponding monofunctional ligands. Thiol to disulfide linkage generated a small dynamic library of bifunctional ligands in the presence of calmodulin, a protein with two independently mobile domains. The binding constant of the bifunctional ligand (disulfide) most amplified by the presence of calmodulin is nearly two orders of magnitude higher than that of the corresponding monofunctional ligand (thiol).     

Chiral Phebox-rhodium complexes as catalysts for asymmetric direct aldol reaction

Chiral bis(oxazolinyl)phenyl-rhodium complexes act as catalysts in the combination of AgOTf for direct aldol reaction of ketones and aromatic aldehydes to give the corresponding β-hydroxyketones in high anti-selectivity and a good to high enantioselectivity up to 91% ee.     

Isotope Probing of the UDP‐Apiose/UDP‐Xylose Synthase Reaction: Evidence of a Mechanism via a Coupled Oxidation and Aldol Cleavage

The C‐branched sugar d ‐apiose (Api) is essential for plant cell‐wall development. An enzyme‐catalyzed decarboxylation/pyranoside ring‐contraction reaction leads from UDP‐α‐d ‐glucuronic acid (UDP‐GlcA) to the Api precursor UDP‐α‐d ‐apiose (UDP‐Api). We examined the mechanism of UDP‐Api/UDP‐α‐d ‐xylose synthase (UAXS) with site‐selectively ²H‐labeled and deoxygenated substrates. The analogue UDP‐2‐deoxy‐GlcA, which prevents C‐2/C‐3 aldol cleavage as the plausible initiating step of pyranoside‐to‐furanoside conversion, did not give the corresponding Api product. Kinetic isotope effects (KIEs) support an UAXS mechanism in which substrate oxidation by enzyme‐NAD⁺ and retro‐aldol sugar ring‐opening occur coupled in a single rate‐limiting step leading to decarboxylation. Rearrangement and ring‐contracting aldol addition in an open‐chain intermediate then give the UDP‐Api aldehyde, which is intercepted via reduction by enzyme‐NADH.