Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• nitroso aldol reactions as a practical tool for the selective introduction of amino or hydroxy moieties at the α-position of a carbonyl function [27][28][29][30]. The last two decades have witnessed an upsurge of interest in the development of organocatalyzed nitroso aldol reactions in addition to the

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• polarity solvents, of a novel class of diametric phosphine gold(I) cavitands characterized by a 1,2,3-alternate geometry. Preliminary catalytic studies were performed on a model cycloisomerization of 1,6-enynes as a function of the relative orientation of the bonded gold(I) nuclei with respect to the

• cycloisomerization of 1,6-enynes as a function of the relative orientation of the bonded gold(I) nuclei with respect to the macrocycle. Further studies are currently under progress to outline the role of the macrocycle and to verify if a possible re-orientation of the gold(I) nuclei towards the center of the

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• digest and metabolic processes [3]. Furthermore, cyclization generally helps to fix the active conformation of a peptide needed to interact with the respective cellular target. Incorporation of non-proteinogenic and unusual amino acids often is related to their biological function. For example, trapoxin

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• in the literature, which generally involve four components. These include one primary amine, two multiple bonds, and one aldehyde function [27]. However, one advantage of our study is that we only used three components since the cinnamaldehyde derivatives 3 played the role of two components at the

• to the more stable aldehyde form C. In the second step, the nitrogen atom of the enamine function attacks the aldehyde carbon atom of the cinnamaldehyde unit in 3, and one water molecule is eliminated to give the desired product. Both steps are accelerated by the presence of the catalyst. In support

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• on reactions believed to involve a direct interaction with the substrate, or with a species (such as a cation) directly formed from the substrate. Sulfonyl chlorides were included in several early considerations of the reaction rates, for processes involving organic substrates, as a function of

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• part in the destruction complex for β-catenin labelling in the canonical Wnt signalling. Loss-of-function mutations in this pathway lead to a dysregulated signal transduction causing cancer [75][76]. All-hydrocarbon stapled peptides comprising amino acids 467 to 481 of the axin CBD had been studied in

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• Haopei Wang Zachary T. Ball Department of Chemistry, Rice University, Houston TX, USA 10.3762/bjoc.17.202 Abstract Photo-responsive modifications and photo-uncaging concepts are useful for spatiotemporal control of peptides structure and function. While side chain photo-responsive modifications

• calculated from crude 1H NMR using residual CD3OD peaks as internal standard. (a) Photocleavage of compound 6 under acidic conditions. Yields determined by 1H NMR using residual CD3OD as an internal standard. (b–d) Selectivity of photocleavage of alkenyl amide 1 as a function of pH. Product percentage of N

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• imines, Schiff bases have the general organic function -C=N- [2], and are known to have a wide range of biological activities, including antioxidant [3], antitubercular [4], antibacterial [5], antimicrobial [6], and antifungal properties [7], in addition to their role as chemosensors [8] (Figure 1

• attributed to a greater electronic conjugation provided by the imine function present in the molecules of the series 3. Photostability and singlet oxygen quantum yield (ΦΔ) assays In order to be efficient for applications in photobiology, organic dyes must be stable when subjected to light irradiation for

• long periods of time. Thus, the photostability parameter is an important characteristic considering that photogenerated singlet oxygen (1O2) can react with a dye molecule, promoting its degradation [32]. Based on the changes in the UV–vis absorption spectra as a function of time, the Schiff base

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• [3,4-d][1,2,3]triazines and their derivatives, for example, were reported to function as anticancer compounds [28][29][32], herbicides [19][20][21], antimicrobials [18], and pest control agents [35]. Several possibilities have been reported to gain the scaffold of pyrazolo[3,4-d][1,2,3]triazines

GlycoBioinformatics

• Kiyoko F. Aoki-Kinoshita,
• Frédérique Lisacek,
• Niclas Karlsson,
• Daniel Kolarich and
• Nicolle H. Packer

Beilstein J. Org. Chem. 2021, 17, 2726–2728, doi:10.3762/bjoc.17.184

• for current global health challenges and to understand just about every biological process. Molecular dynamic modeling to understand how glycans interact with biomolecules visualizes and allows the development of hypotheses regarding the function of glycans to be tested at a molecular level. The

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• (treatment with excess methyllithium) to give the corresponding alkaloids with free N–H function. This dual use of the ethoxycarbonyl group shortens the synthetic routes to hydroxylated 1-benzyltetrahydroisoquinolines significantly. Not surprisingly, these ten alkaloids did not show noteworthy effects on

• ]. This prompted us to investigate the generality of this approach (dual function of the ethoxycarbonyl residue as activating group for the Pictet–Spengler reaction and as protective group for phenolic groups). This effort ended up with short and effective total syntheses of ten racemic 1-benzyl-1,2,3,4

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• -based lactol. This is a necessary requirement to produce the desired stereochemistry in the product. It was extensively reported that the β-selectivity could be due to the formation of an oxonium ion, which is stabilized through anchimeric assistance of the ʟ-menthyl ester function. The method requires

• stereoselective N-glycosylation. We hypothesize that because of the Lewis acid character, ZrCl4 could most likely form a precomplex with the sulfur atom of the oxathiolane ring, as in IV. The presence of the chiral ʟ-menthyl ester auxiliary function assists the complexation with ZrCl4 in a specific orientation

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• itself, in which the carboxylic function acts as an ancillary hydrogen-bond donor for the direction of one of the reagents [9]. Amines serve as basic units and nucleophilic components capable of carbonyl compounds activation via enamine or iminium ion formation [10][11]. In particular, pyrrolidine became

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• -moderate yields but with ≥74% ee, while the α-amino ketone products 15 could be obtained in nearly quantitative yields and variable ee, from 53% to 98% [6]. A fifth example of an enantioselective α-ketol rearrangement provides a twist by demonstrating the ability to function on substrates protected as

• use of silica gel and montmorillonite K 10 as catalysts is that they function under neutral conditions, permitting the use of acid-sensitive groups, such as silyl ethers. For example, 101 was converted to 102 in 70% and 96% yield, respectively, with silica gel and montmorillonite K 10, but with

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• specific pH while using materials compatible with the colon. Also, assessing swelling as a function of NaCl concentration began to explore osmotic interactions of hydrogels, adding to the consideration of environmental conditions and providing data in a region often overlooked in these types of studies. A

• polyamidoamine (PAMAM) dendrimers have been shown to be effective for minimally invasive drug delivery [83]. The reinforced cryogels main function was to provide scaffolding for cell growth and also incorporated the anti-inflammatory corticosteroid drug betamethasone sodium phosphate (BSP) for delivery when

• shows promise to solving these problems and enhancing skin substitutes [7]. An optimal bio-scaffold would have to be biocompatible, biodegradable, have a high pore connectivity and swelling ratio as its function is to promote cell growth and act as a nucleus for cell migration. Moreover, ideally it

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• enaminones 15 to pyrrolizines 19 was determined by TLC monitoring of the reaction mixture after successive time intervals. A fairly accurate estimate of the reaction time as a function of the changing acyl substituent could thus be obtained to within 30 seconds. As can be seen from Table 2, we observed a

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• photoinduced copper-catalyzed reactions. Copper photoredox catalysts are powerful photocatalysts used for cross-coupling reactions. Their function is based on the strong reducing power of copper complexes and the ability of copper complexes to coordinate substrates or trap reactive intermediates. The

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• proposed a plausible mechanism for the reaction of 6a with diluted HCl (Scheme 10). The mechanism consists of four major steps: the first step is an acid-catalyzed hydrolysis of the acetal function in 6a to afford aldehyde 15; the second step is the enolization of the aldehyde 15 to form the tautomeric

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• are otherwise highly conserved. Site-directed mutagenesis experiments for these residues are reported that showed different effects, resulting in some cases in an improved catalytic activity, but in other cases in a loss of enzyme function. For other enzyme variants a functional switch was observed

• ratios as for the wildtype, which may again have steric reasons. Taken together, these results demonstrate that residues found to be highly conserved and known to be critical for enzyme function in type I TPSs can in some cases be naturally substituted by other residues without consequences on the enzyme

• from A222V (37% ee), A222L (7% ee) and A222I (32% ee). Conclusion Terpene synthases contain several well-known highly conserved motifs and single residues that are believed to be generally important for structure and function. As we show here, in special cases such as the sestermobaraene synthase SmTS1

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• have shown great promise as these drugs inhibit the function of mitochondria while showing overall reduced systemic toxicity. PENAO (4-(N-(S-penicillaminylacetyl)amino)phenylarsenonous acid) [2][3], a trivalent arsenical drug, was developed by Hogg and co-workers and is currently in clinical trials [4

• , it is more important to understand how TPP is presented on the surface of these PISA particles. In order for TPP to fulfil its function, the surrounding of the ligand needs to be considered. Cartoons are widely used in the drug delivery literature, often showing the targeting ligand readily available

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• scaffold. Keywords: deazapurines; heterocycles; pyrrolopyrimidines; queuosine; RNA cofactors; RNA methylation; Introduction Methylated preQ1 has attracted much attention recently because this compound has been found to function as cofactor for the conserved fold of a non-coding RNA, namely the preQ1

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• C1 position. Analogously to the Pictet–Spengler cyclization, the group initially speculated that the thiourea catalyst 6 interacts with the carbonyl function of the amide intermediate I and, thus, a SN2-type mechanism via hydrogen bonding catalysis was proposed. A similar bidentate carbonyl

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• developments, which enables a diverse range of previously inaccessible organic transformations in milder reaction conditions [31][32][33][34][35][36][37][38][39][40]. Here, by absorbing visible light, a photocatalyst can function as a single-electron redox mediator through an oxidative or reductive quenching

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• thermoresponsive behavior of polymers is governed by oriented polymer–polymer interactions, such as hydrogen bonding or electrostatic interactions. As a function of temperature, these attractive interactions are formed and contribute to phase separation (T < UCST) or are increasingly destabilized and allow

• function of composition. This region cannot be realized by “equilibrium” experiments and can only be captured mathematically. These points are also called spinodal points. In addition, two further minima exist. By applying the double tangent to these two points C and D, the composition of the coexisting

• Alexander [121]. In this theoretical work scaling laws were derived for uniformly stretched neutral polymer chains in nonpolar solvents that form a brush with fairly uniform density (“box-model”). The scaling laws allow the description of the swollen layer thicknesses as a function of the grafting density

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• describing their preparation. An evaluation of different approaches has been achieved, allowing to define the best strategies to introduce diversity on both the malonic position and the ester function. A classical alkylation step of a malonate by an alkyl halide followed by a monosaponification gave access

• to reagents bearing different substituents at the malonic position, including functionalized derivatives. On the other hand, the development of a monoesterification step of a substituted malonic acid derivative proved to be the best entry for diversity at the ester function, rather than the use of an

• ][38]. Despite its efficiency, this strategy remains limited regarding the nature of the alkoxy group of the ester function (generally Me or Et), as it arises from the parent malonate. In order to introduce diversity at this position, the privileged route is based on the opening of a Meldrum's acid