Asymmetric Organocatalytic Cyclization and Cycloaddition Reactions

During the resorbable-polymer-boom of the 1970s and 1980s, polycaprolactone (PCL) was used in the biomaterials field and a number of drug-delivery devices. Its popularity was soon superseded by faster resorbable polymers which had fewer perceived disadvantages associated with long term degradation (up to 3-4 years) and intracellular resorption pathways; consequently, PCL was almost forgotten for most of two decades. Recently, a resurgence of interest has propelled PCL back into the biomaterials-arena. The superior rheological and viscoelastic properties over many of its aliphatic polyester counterparts renders PCL easy to manufacture and manipulate into a large range of implants and devices. Coupled with relatively inexpensive production routes and FDA approval, this provides a promising platform for the production of longer-term degradable implants which may be manipulated physically, chemically and biologically to possess tailorable degradation kinetics to suit a specific anatomical site. This review will discuss the application of PCL as a biomaterial over the last two decades focusing on the advantages which have propagated its return into the spotlight with a particular focus on medical devices, drug delivery and tissue engineering.

The return of a forgotten polymer : Polycaprolactone in the 21st century

National Institute of General Medical Sciences (U.S.) (Center for Integrative Synthetic Biology Grant P50GM098792)

A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes

Whereas noble metal compounds have long been central in catalysis, Earth-abundant metal-based catalysts have in the same time remained undeveloped. Yet the efficacy of Earth-abundant metal catalysts was already shown at the very beginning of the 20th century with the Fe-catalyzed Haber–Bosch process of ammonia synthesis and later in the Fischer–Tropsch reaction. Nanoscience has revolutionized the world of catalysis since it was observed that very small Au nanoparticles (NPs) and other noble metal NPs are extraordinarily efficient. Therefore the development of Earth-abundant metals NPs is more recent, but it has appeared necessary due to their “greenness”. This review highlights catalysis by NPs of Earth-abundant transition metals that include Mn, Fe, Co, Ni, Cu, early transition metals (Ti, V, Cr, Zr, Nb and W) and their nanocomposites with emphasis on basic principles and literature reported during the last 5 years. A very large spectrum of catalytic reactions has been successfully disclosed, and catalysis has been examined for each metal starting with zero-valent metal NPs followed by oxides and other nanocomposites. The last section highlights the catalytic activities of bi- and trimetallic NPs. Indeed this later family is very promising and simultaneously benefits from increased stability, efficiency and selectivity, compared to monometallic NPs, due to synergistic substrate activation.

The recent development of efficient Earth-abundant transition-metal nanocatalysts

Despite the fact that halogenation of alkenes has been known for centuries, enantioselective variants of this reaction have only recently been developed. In the past three years, catalytic enantioselective versions of halofunctionalizations with the four common halogens have appeared and although important breakthroughs, they represent just the very beginnings of a nascent field. This Minireview provides a critical analysis of the challenges that accompany the development of general and highly enantioselective halofunctionalization reactions. Moreover, the focus herein, diverges from previous reviews of the field by identifying the various modes of catalysis and the different strategies implemented for asymmetric induction.

Catalytic, Asymmetric Halofunctionalization of Alkenes—A Critical Perspective

Environmental remediation relies mainly on using various technologies (eg, adsorption, absorption, chemical reactions, photocatalysis, and filtration) for the removal of contaminants from different environmental media (eg, soil, water, and air) The enhanced properties and effectiveness of nanotechnology-based materials makes them particularly suitable for such processes given that they have a high surface area-to-volume ratio, which often results in higher reactivity This review provides an overview of three main categories of nanomaterials (inorganic, carbon-based, and polymeric-based materials) used for environmental remediation The use of these nanomaterials for the remediation of different environmental contaminants—such as heavy metals, dyes, chlorinated organic compounds, organophosphorus compounds, volatile organic compounds, and halogenated herbicides—is reviewed Various recent examples are extensively highlighted focusing on the materials and their applications

https://www.mdpi.com/1420-3049/23/7/1760/pdf/1

Nanotechnology for Environmental Remediation: Materials and Applications.

A reagent controlled organocatalytic enantioselective chlorolactonization reaction has been developed. Several 4-aryl pentenoic acids were cyclized in the presence of 0.1 equiv of (DHQD)2PHAL, employing various N-chlorinated hydantoins as the terminal chlorenium source. Ten examples are presented with selectivities ranging from 43 to 90% ee. This work represents the first example of an enantioselective reagent-controlled chlorolactonization that approaches synthetically useful enantioselectivities.

An organocatalytic asymmetric chlorolactonization.

Reuterin is an antimicrobial compound produced by Lactobacillus reuteri, and has been proposed to mediate, in part, the probiotic health benefits ascribed to this micro-organism. Despite 20 years of investigation, the mechanism of action by which reuterin exerts its antimicrobial effects has remained elusive. Here we provide evidence that reuterin induces oxidative stress in cells, most likely by modifying thiol groups in proteins and small molecules. Escherichia coli cells subjected to sublethal levels of reuterin expressed a set of genes that overlapped with the set of genes composing the OxyR regulon, which senses and responds to various forms of oxidative stress. E. coli cells mutated for oxyR were more sensitive to reuterin compared with wild-type cells, further supporting a role for reuterin in exerting oxidative stress. The addition of cysteine to E. coli or Clostridium difficile growth media prior to exposure to reuterin suppressed the antimicrobial effect of reuterin on these bacteria. Interestingly, interaction with E. coli stimulated reuterin production or secretion by L. reuteri, indicating that contact with other microbes in the gut increases reuterin output. Thus, reuterin inhibits bacterial growth by modifying thiol groups, which indicates that reuterin negatively affects a large number of cellular targets.

The antimicrobial compound reuterin (3-hydroxypropionaldehyde) induces oxidative stress via interaction with thiol groups.

Stereodefined carbon–halogen bonds are ubiquitous in nature with several natural products exhibiting this motif. While the biogenetic origins of this unique chiral functionality has been a subject of several investigations in the past, attempts by organic chemists to forge the carbon–halogen bond stereoselectively have largely been unsuccessful. This problem has come into focus only recently. Several elegant reports of asymmetric halogenations of alkenes and alkynes followed by an intramolecular attack of a pendant nucleophile have appeared in the literature in the last decade. Kang et al. reported a cobalt–salen catalyzed iodoetherification reaction. An asymmetric fluorocyclization of allyl silanes mediated by a cinchona alkaloid dimer was reported by Gouverneur and co-workers. Tang and co-workers disclosed an asymmetric bromolactonization of enynes catalyzed by a cinchona alkaloid derived urea; other bromolactonizations have also appeared following the disclosure of their report. More recently, Veitch and Jacobsen reported an asymmetric iodolactonization reaction mediated by chiral thiourea catalysts. Polyene cyclizations induced by chiral halonium ions have also been realized as reported by the research groups of Ishihara and Snyder. However, given the fledgling nature of this research area, one may find it easy to highlight the many drawbacks and limitations even in the present state of the art—for example, the relatively large catalyst loadings (superstoichiometric quantities in some cases) to achieve meaningful levels of enantioselectivity or the lack of a robust catalytic system that can catalyze a number of diverse reactions rather than one specific reaction. Moreover, efficient asymmetric chlorocyclizations have remained underdeveloped. This situation is attributable, at least in part, to the highly reactive nature of chloronium ions, which are known to exist in equilibrium with the corresponding carbocation rather than exclusively as cyclic chloronium ions, thus making the development of chlorocyclizations a formidable challenge. Our research group has recently reported the catalytic asymmetric chlorolactonization of alkenoic acids. Herein, we disclose the efficient halocyclization of unsaturated amides to furnish chiral heterocycles. Furthermore, these heterocycles have been transformed into useful chiral building blocks such as amino alcohols. Chiral heterocycles such as oxazolines and dihydrooxazines are commonly encountered motifs in natural products, molecules of pharmaceutical interest, and in several chiral ligands. Their syntheses, however, usually employ stoichiometric quantities of chiral amino alcohols. With only one precedented method to access these molecules in a catalytic asymmetric fashion, we were intrigued by the possibility of one-step access to these versatile chiral heterocycles by a catalytic asymmetric halocyclization of easily accessed unsaturated amides. We chose the conversion of benzamide 1 into oxazoline 2 as our initial test reaction. Among the several ligands screened for the test reaction, (DHQD)2PHAL emerged as the best candidate, thus affording the desired oxazoline 2 in 57% ee (Table 1, entry 1) with DCDMH as the terminal chlorine source. Reactions with other chlorenium sources

Daniel C. Whitehead

Papers

Nanotechnology for Environmental Remediation: Materials and Applications.

An organocatalytic asymmetric chlorolactonization.

The antimicrobial compound reuterin (3-hydroxypropionaldehyde) induces oxidative stress via interaction with thiol groups.

A catalytic asymmetric chlorocyclization of unsaturated amides.

On the chlorenium source in the asymmetric chlorolactonization reaction.