Search results for "combinatorial"

Carbohydrate Scaffolds for Combinatorial Syntheses That Allow Selective Deprotection of All Four Positions Independent of the Sequence

2004

Recent Advances in Enantioselective Desymmetrizations of Prochiral Oxetanes

2021

Abstract Strain relief of oxetanes offers a plethora of opportunities for the synthesis of chiral alcohols and ethers. In this context, enantioselective desymmetrization has been identified as a powerful tool to construct molecular complexity and this has led to the development of elegant strategies on the basis of transition metal, Lewis acid, and Brønsted acid catalysis. This review highlights recent examples that harness the inherent reactivity of prochiral oxetanes and offers an outlook on the immense possibilities for synthetic application.

An efficient β-turn directed cyclization of simple peptidomimetics

1999

Abstract Chiral polyaza[n]para- and metacyclophanes are easily assembled starting from the appropriate bis(bromomethyl)arene and diamides obtained from aminoacids and alkylidenediamines. The corresponding ortho-derivatives could not be obtained. Molecular dynamics calculations suggest that those results can be explained through the participation of a β-turn like structure in the open chain intermediate, which is only important for para- and meta-derivatives.

Pillar[n]arenes-a Novel, Highly Promising Class of Macrocyclic Host Molecules

2014

Since 2008 a new field of supramolecular chemistry has developed rapidly: the chemistry of pillar[n]arenes. These “younger brothers and sisters” of calixarenes are conveniently accessible and extremely guest-friendly. Guests from many different classes of organic compounds are welcome. Nevertheless, a high selectivity for the threading of guest molecules in the macrocyclic cavities can be achieved. The complex stability is characterized by association constants Ka between 10 and 1×108 M−1. The rate constants of the threading vary over several orders of magnitude. The focus of this article lies on the preparation (sections 2 and 3) and the structures (section 4) of pillar[n]arenes (n=5–10) i…

Design, synthesis and biological evaluation of novel stilbene-based antitumor agents

2008

A series of novel stilbene derivatives has been synthesized and studied with the main goal to investigate SAR of the amino compound 1a, as well as to improve its water solubility, a potentially negative aspect of the molecule that could be a serious obstacle for a pre-clinical development. We have obtained derivatives with good cytotoxic activity, in particular, the derivatives 5c and 6b could represent two novel leads for further investigation. Compound 8b, a morpholino-carbamate derivative, prodrug of 1a, has a very good solubility in water, and is active in suppressing growth of tumor cells at a concentration of 5000 nM, which is a concentration 100 times higher than the parent stilbene …

Identification of 2-(thiophen-2-yl)acetic Acid-Based Lead Compound for mPGES-1 Inhibition.

2021

We report the implementation of our in silico/synthesis pipeline by targeting the glutathione-dependent enzyme mPGES-1, a valuable macromolecular target in both cancer therapy and inflammation therapy. Specifically, by using a virtual fragment screening approach of aromatic bromides, straightforwardly modifiable by the Suzuki-Miyaura reaction, we identified 3-phenylpropanoic acid and 2-(thiophen-2-yl)acetic acid to be suitable chemical platforms to develop tighter mPGES-1 inhibitors. Among these, compounds 1c and 2c showed selective inhibitory activity against mPGES-1 in the low micromolar range in accordance with molecular modeling calculations. Moreover, 1c and 2c exhibited interesting IC…

Use of Bile Acids in Pharmacological and Supramolecular Applications

2004

Bile acid-based structures have become increasingly important in different fields of chemistry over recent years, having found applications in pharmacology, supramolecular chemistry and nanoscience. Some interesting studies concerning these applications are reviewed, together with the latest developments in synthetic and analytical methods for bile acid-derived frameworks. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Helicates with Ether-Substituted Catechol Esters as Ligands

2020

European journal of organic chemistry 2020(32), 5161-5172 (2020). doi:10.1002/ejoc.202000843

Hydrolase–like catalysis and structural resolution of natural products by a metal–organic framework

2020

[EN] The exact chemical structure of non-crystallising natural products is still one of the main challenges in Natural Sciences. Despite tremendous advances in total synthesis, the absolute structural determination of a myriad of natural products with very sensitive chemical functionalities remains undone. Here, we show that a metal-organic framework (MOF) with alcohol-containing arms and adsorbed water, enables selective hydrolysis of glycosyl bonds, supramolecular order with the so-formed chiral fragments and absolute determination of the organic structure by single-crystal X-ray crystallography in a single operation. This combined strategy based on a biomimetic, cheap, robust and multigr…

Novel antiproliferative chimeric compounds with marked histone deacetylase inhibitory activity.

2014

Given our interest in finding potential antitumor agents and in view of the multifactorial mechanistic nature of cancer, in the present work, taking advantage of the multifunctional ligands approach, new chimeric molecules were designed and synthesized by combining in single chemical entities structural features of SAHA, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives previously obtained by us and endowed with antiproliferative and pro-apoptotic activity. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on different tumor cell lines, as well as their HDACs inhibitio…