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Ferrocenyl conjugated oxazepine/quinoline derivatives were presented through the reaction of hexadehydro-Diels-Alder (HDDA) generated arynes with ferrocenyl oxazolines under mild conditions via ring-expanding or rearrangement processes. Water molecule participated in this unexpected rearrangement process to produce quinoline skeletons, and DFT calculations supported a ring-expanding and intramolecular hydrogen migration process for the formation of oxazepine derivatives. Two variants of this chemistry, expanded the reactivity between ferrocenyl conjugated substances and arynes, further providing an innovative approach for the synthesis of ferrocene derivatives. [ABSTRACT FROM AUTHOR]

Two new chiral 1,2,3‐triazole‐containing macrocyclic oligoamides (i. e.: triazolopeptoid 4 and 5) were obtained through solid‐phase synthesis of linear precursors followed by high dilution macrocyclization reaction. Theoretical (DFT) and spectroscopic (NMR) studies revealed the intricate interplay between the Nα‐chiral side chains and their conformational attitudes. BH3‐mediated reduction of the tertiary amide groups of known 1–3 and newly synthesized 4 gave novel azamacrocycles 6–9. Detection of borane complexes of azamacrocycles 6 and 9 (i. e.: 10 and 11), corroborated by X‐ray diffraction studies, demonstrated the peculiar properties of 1,2,3‐triazole‐containing macrorings. [ABSTRACT FROM AUTHOR]

This review describes the advances of heterogenous phase‐transfer catalysts onium‐based and their importance from a sustainable point of view. Although heterogeneous phase‐transfer catalysts have shown incredible advantages in many organic reactions, examples of supported phase‐transfer catalysts onium‐based are still limited. In this review, we will examine the most common supports, including polymers, clays, and inorganic materials. Additionally, new recent developments in carbon materials application as efficient heterogeneous phase‐transfer catalysts in water will be reported, opening a new route toward green and sustainable procedures. Furthermore, considering the ever‐growing interest in asymmetric synthesis we wish to discuss the important achievements in the field of chiral heterogeneous phase‐transfer catalysts. [ABSTRACT FROM AUTHOR]

A method for the asymmetric synthesis of phthalides containing a stereogenic γ‐carbon has been described. The protocol, based on the arylogous Michael addition to chiral alkenoyl oxazolidinones catalyzed by a crown ether under phase‐transfer conditions does not require anhydrous conditions and uses commercially available materials. A complete syn‐stereocontrol is achieved and facial diastereoselectivities are moderate to excellent (62:38 to 99:1 dr). Purification of the major diastereomer by chromatography and selective cleavage of the chiral auxiliary affords enantiopure Michael products. The protocol has been applied to the formal synthesis of escitalopram. [ABSTRACT FROM AUTHOR]

Multivalency represents an appealing option to modulate selectivity in enzyme inhibition and transform moderate glycosidase inhibitors into highly potent ones. The rational design of multivalent inhibitors is however challenging because global affinity enhancement relies on several interconnected local mechanistic events, whose relative impact is unknown. So far, the largest multivalent effects ever reported for a non‐polymeric glycosidase inhibitor have been obtained with cyclopeptoid‐based inhibitors of Jack bean α‐mannosidase (JBα‐man). Here, we report a structure‐activity relationship (SAR) study based on the top‐down deconstruction of best‐in‐class multivalent inhibitors. This approach provides a valuable tool to understand the complex interdependent mechanisms underpinning the inhibitory multivalent effect. Combining SAR experiments, binding stoichiometry assessments, thermodynamic modelling and atomistic simulations allowed us to establish the significant contribution of statistical rebinding mechanisms and the importance of several key parameters, including inhitope accessibility, topological restrictions, and electrostatic interactions. Our findings indicate that strong chelate‐binding, resulting from the formation of a cross‐linked complex between a multivalent inhibitor and two dimeric JBα‐man molecules, is not a sufficient condition to reach high levels of affinity enhancements. The deconstruction approach thus offers unique opportunities to better understand multivalent binding and provides important guidelines for the design of potent and selective multiheaded inhibitors. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) is a common medical imaging technique that provides three‐dimensional body images. MRI contrast agents improve image contrast by raising the rate of water proton relaxation in specific tissues. Peptides and peptidomimetics act as scaffolds for MRI imaging agents because of their increased size and offer the possibility to engine a higher hydration value within the design. The design of a new Gd‐based contrast agent must take into account high stability constants to avoid free Gd(III), with the subsequent nephrotoxicity, and high relaxivity values. This review analyzes various synthetic approaches, reports studies of relaxometric parameters, and focuses on the description and application of Gd(III)‐chelates based on peptide and peptidomimetic scaffolds. In addition, the X‐ray molecular structures of three DOTA complexes will be reported to emphasize the necessity of using the X‐ray diffraction analysis to identify the coordination sphere of the metals and the mechanism of action of the compounds. [ABSTRACT FROM AUTHOR]

Chiral β-azido- and β-cyanocarbonyl compounds are extremely useful building blocks in asymmetric synthesis, thanks to the manyfold reactivity of their functional groups. The enantioselective synthesis of such compounds, until the beginning of the 21st century, has been mostly achieved using transition-metal chiral catalysts. The explosion of enantioselective organocatalysis, however, has enabled the development of efficient metal-free methodologies with significant benefits in terms of costs and environmental safety. An overview of the advances made in recent years in this field is herein presented. [ABSTRACT FROM AUTHOR]

Despite the great advantages of peptidomimetic scaffolds, there are only a few examples of their application in the field of asymmetric catalysis. Peptidomimetic scaffolds offer numerous advantages related to their easy preparation, modular and tunable structures, and biomimetic features, which make them well suited as chiral catalysts. This review underlines the structure–function relationship for catalytic properties towards efficient enantioselective catalysis. [ABSTRACT FROM AUTHOR]

Enantiomorphic right- and left-handed polyproline type I helices in four cyclic dodecapeptoids with methoxyethyl and propargyl side chains are observed for the first time by single crystal X-ray diffraction. The peculiar absence of NH⋯OC hydrogen bonds in peptoids unveils the role of intramolecular backbone-to-backbone CO⋯CO interactions and CH⋯OC hydrogen bonds in the stabilization of the macrocycle conformation. Moreover, intramolecular backbone-side chain C5 CH⋯OC hydrogen bonds emerge as a stabilizing factor. [ABSTRACT FROM AUTHOR]

Cyclic peptoids are biocompatible/biodegradable cyclooligomers constituted by N-substituted glycines showing high binding constants with the first group alkali metals (Ka ∼ 106 for Na+, Li+ and K+) in organic solvents. Three new metallated species bearing N-benzyl groups as side chains (a cyclic pentamer, [1·2Na]2+, and two cyclooctamer [3·Na]+ and [3·2Na]2+ peptoids) were synthesized together with the known N-perbenzylated sodiated cyclohexamer [2·Na]+ and [2·2Na]2+. Na+ complexes were investigated by means of spectroscopic (NMR), computational (DFT) and X-ray crystallographic studies. The first application of these complexes as catalysts in the ring opening polymerization (ROP) of L -lactide (L -LA) was examined. Our studies suggest that, for the intrinsic properties of the catalytic site (revealed by steric topographic maps) the homooligomeric pentamer complex [1·2Na]2+ is the most active member of the cyclooligomeric family. [ABSTRACT FROM AUTHOR]

Two families of hexameric cyclic peptoids decorated with linear N‐alkyl and alternated N‐alkyl/N‐benzyl side chains (2 a–d and 3 a–c, respectively) were designed and synthesized in order to correlate their logP values (from 2.55 to 6.83) to their ionophoric activities. The present contribution confirms the general ability of hexameric cyclic peptoids to behave as efficient cation carriers, corroborates their preference for Na+ ion, among the tested alkali metals, and suggests a Na+/H+ antiport transport mechanism (rate limited by the transport of the proton) for these new ionophores. Our observations indicate that in order to attain an efficient ionophoric activity, a narrow range of liphophilicity is required (4

The solid state assembly of two cyclic hexapeptoids decorated respectively with five and six carbon N-alkyl side chains is analyzed by single crystal X-ray diffraction, intermolecular energies and lattice energy calculations. Thermal analysis and variable temperature X-ray powder diffraction were also carried out to analyze their thermal behaviour. The crystal structures of the two compounds feature architectural similarities, but also small relevant differences due to side chains-to-side chains interactions, which can explain the observed differences in the thermal properties. The compound with N-pentyl side chains exhibits a phase transition upon cooling down from room temperature to 100 K, while that with N-hexyl side chains features no phase transformation on cooling, instead a phase transformation occurs at 335 K upon heating. [ABSTRACT FROM AUTHOR]

The first highly enantioselective arylogous Michael reaction (AMR) of 3‐unsubstituted phthalides has been described. This phase‐transfer methodology, which uses catalytic amounts of KOH/18‐crown‐6 catalyst in mesitylene in the presence of N,O‐bis(trimethylsilyl)acetamide (BSA), gives access to a broad range of 3‐monosubstituted phthalides with high levels of syn diastereoselectivity and good yields, starting from 3‐unsubstituted derivatives and diverse α,β‐unsaturated carbonyl compounds. The reaction also applies to unactivated 3‐alkyl phthalides to afford 3,3‐dialkyl derivatives. A plausible mechanism has been suggested. DFT analysis of possible transition states gives a rationale of the high syn diastereoselectivity observed and its correlation with the solvent's dielectric constant. [ABSTRACT FROM AUTHOR]

The introduction and development of neutral macrocyclic hosts capable of complexing ions within their pre-organized cavity, has been of utmost importance in supramolecular chemistry. Their ability to form stable organic-soluble metal-macrocycle complexes opened up the way to their application in phase-transfer catalysis (PTC) as a viable alternative to quaternary onium salts. In particular, their conformationally rigid preorganized backbone, accommodating organic substrates in defined orientations, promotes highly efficient stereoselective reactions. This short review summarizes the applications of neutral macrocyclic hosts in stereoselective PTC, highlighting the difference and possible complementarity with quaternary ammonium salts. 1 Introduction 2 Crown Ethers and Related Coronands 2.1 Enantioselective PTC with Chiral Macrocyclic Coronands 2.2 Enantioselective PTC Reactions Catalyzed by Chiral Quaternary Ammonium Salts with Achiral Crown Ether Co-catalysts 3 Cyclic Peptoids 4 Miscellaneous Chiral Macrocyclic Hosts 5 Summary and Outlook. [ABSTRACT FROM AUTHOR]

The recognition abilities of chiral calixarene hosts toward alkali cation guests have been exploited for the first time in asymmetric phase-transfer catalysis. The binding affinities of a series of chiral α-methylbenzylamine-derived calix[4]areneamides toward Na+ guest have been determined by ¹H NMR spectroscopic titration experiments. The good apparent association constant values are consistent with the macrocycles' catalytic efficiency in the asymmetric alkylation reaction of N-(diphenylmethylene) glycine esters under phase-transfer conditions. [ABSTRACT FROM AUTHOR]

Nonionic, chiral macrocyclic peptoids are efficient phasetransfer catalysts in the C-4 enantioselective alkylation of 2-[4-(trifluoromethyl) phenyl]-2-oxazoline-4-carboxylic acid esters. Screening of the structural features of cyclic peptoids, namely the ring size, symmetry elements, number of proline residues, and substituents on the side chains, showed that the alternated N-(4-methoxybenzyl)glycine/L-proline cyclohexapeptoid is the optimal catalyst (good yields and up to 75% ee) for the stereocontrolled construction of α-alkylated serine tert-butyl esters. [ABSTRACT FROM AUTHOR]

A critical summary on the discovery of the nineteen members of the phakellistatin family (phakellistatin 1-19), cytotoxic proline-rich cyclopeptides of marine origin, is reported. Isolation, structural elucidation, and biological properties of the various-sized natural macrocycles are described, along with the total syntheses and the enigmatic issues of the cytotoxic activity reproducibility. [ABSTRACT FROM AUTHOR]

The effects of substituents and cavity size on catalytic efficiency of proline-rich cyclopeptoids under phase-transfer conditions were studied. High affinity constants (Ka) for the sodium and potassium cations, comparable to those reported for crown ethers, were observed for an alternated N-benzylglycine/l-proline hexameric cyclopeptoid. This compound was found to catalyze the alkylation of N-(diphenylmethylene)glycine cumyl ester in values of enantioselectivities comparable with those reported for the Cinchona alkaloid ammonium salts derivatives (83-96% ee), and with lower catalyst loading (1-2.5% mol), in the presence of a broad range of benzyl, allyl and alkyl halides. [ABSTRACT FROM AUTHOR]

The first application of cyclopeptoids in asymmetric phase-transfer catalysis was examined. A small library of nine alternating N-substituted-glycine and proline hexacyclopeptoids was tested in the enantioselective alkylation of N-(diphenylmethylene)glycine tert-butyl ester. The presence of an N-arylmethyl side chain in the catalyst was found to be crucial for the synthesis of α-amino acids with up to 73 % ee. [ABSTRACT FROM AUTHOR]

A library of proline-containing cyclopeptoids is prepared, characterized and their complexing ability is evaluated. [ABSTRACT FROM AUTHOR]

Nine alternating N-substituted-glycine and proline hexacyclopeptoids are employed in the alkylation of N-(diphenylmethylene)glycine tert-butyl ester. [ABSTRACT FROM AUTHOR]