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

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• strategy for the enanantioselective conjugate addition of amino acid derivatives for this reaction remains an unmet goal. Our group previously described a chiral cyclopropenimine catalyst that displayed outstanding reactivity for addition reactions of glycine imines [40][41]. We hypothesized that this

• the reaction (Table 2, entry 12), the incorporation of this substituent led to a nearly total loss in selectivity. Although we have not examined this specific reaction computationally, it is reasonable to expect that it shares many similarities to the corresponding glycine imine addition we previously

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• relative to the downregulation of the reference ASO (Oblimersen) [91]. In an entirely different approach, the 2’-amino group of amino-LNA-thymine (amino-LNA-T) has been explored as an attachment point for various cationic groups. As one example, amino acids such as glycine, lysine, and proline in different

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• positions of the backbone α-Modified PNA: Adding substituents to the N-(2-aminoethyl)glycine backbone has been an obvious starting point for PNA modification. Nielsen and co-workers were the first to replace the glycine residues in PNA backbone with various chiral amino acids [67][68]. Most of these α

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• of Technology Indore, Khandwa Road, Simrol, Indore-453 552, India, School of Chemical Sciences, National Institute of Science Education and Research, Bhubaneswar-752 050, Odisha, India 10.3762/bjoc.17.101 Abstract 1,5-Disubstituted indole-2-carboxaldehyde derivatives 1a–h and glycine alkyl esters 2a

• the literature, there is only a limited number of direct synthetic procedures to prepare γ-carbolines till date [28], and this gives a cutting edge advantage to our new protocol wherein a solvent and metal-free direct access to the γ-carboline core from substituted indole-2-aldehyes and glycine ester

• . Herein, we report an interesting observation for conversion of substituted indole-2-aldehydes 1 to 1-indolyl-3,5,8-substituted γ-carbolines 3 by a cascade imination-heterocylization pathway when treated with the salt glycine methyl ester hydrochloride (2a) in the presence of a base. Earlier in the

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• ] developed a visible-light-induced [3 + 2] cycloaddition reaction between glycine derivatives 57 and aryl epoxides 58, which can efficiently prepare a series of multisubstituted 1,3-oxazolidines 59 at room temperature (Scheme 20). The strategy can be applied smoothly to an extensive range of glycine

• -functionalization of glycine derivatives. The construction of C–C bonds As a crucial element in the construction of various organic scaffolds, the formation of C–C bonds remains a hot topic in the field of synthetic organic chemistry. The conventional approaches of C–C-bond construction typically employ transition

• absorption of EDA complex in the visible-light region. In 2020, Xu and colleagues [39] proposed a visible-light-promoted alkylation reaction using Katritzky salts such as 128 and glycine derivative 127 (or glycine segments in peptides) initiated by an EDA complex. This successfully realized the simple

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• given in Scheme 9 [87]. On this pathway for the synthesis of conjugates 19 and 20, acid 18 is cross-linked with a peptide component using a milder carbodiimide method via the starting methanofullerene 17. Similar to Scheme 8, fullerene adducts 21 and 22 with glycine and phenylalanine, respectively, were

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• serine–glycine (SG)n segments rather than classical poly(oxyethylene) linkers between the lipid polar head and a targeting ligand were proposed for the liposome-mediated, selective delivery of anticancer drugs. Here, we report the synthesis of perfluoroalkylated lipopeptides (F-lipopeptides) bearing two

• proposed for the preparation of functional drug carriers for clinical applications [25][28][29]. In order to alleviate the steric hindrance effect of PEG chains, a novel spacer consisting of alternating serine–glycine sequences (SG)n was introduced between the ligand and lipid within the molecular

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• -aminophosphonodichloride 92 with phenol and methyl (S)-2-hydroxypentanoate (18). All synthetic phosphonodepsipeptides 99, 102, and 104 were considered as glutathione-analogue phosphonopeptides as mechanism-based inhibitors of γ-glutamyl transpeptidase for probing the cysteinyl-glycine binding site (Scheme 16) [31

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• first protein-biosynthesis-generated structures are based on variable backbone elements; proline (cyclic and chiral), glycine (acyclic and achiral) or alanine (acyclic and chiral). Subsequent acquisition of the functional side-chains for this repertoire led to the recruitment of amino acids that are

• sequences (Figure 2A and Figure 2B). This way of reasoning makes proline (as well as glycine) a kind of foreign structural element in the predominantly alanine-based protein architectures, or in other words, it is an alien in the “alanine world”. How could proline be replaced in protein structures of living

• class IIa AARSs. In addition to the main activation and charging steps described above, the bacterial ProRS (gene proS) performs a few additional proofreading steps. Alanine and glycine are amino acids smaller than proline but with a similar polarity, and they can be activated by ProRS. If this happens

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• interactions but have a high propensity to form interprotein interactions. In contrast, serine, threonine, asparagine (polar uncharged), alanine, valine, isoleucine (hydrophobic), cysteine, proline, and glycine are less likely to form interprotein interactions and bifurcated interactions. The binding mode in

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• membrane-bound receptors interact strongly with short peptidic segments of a larger protein chain, for example, recognition of the RGD sequence (arginine–glycine–aspartic acid; Arg–Gly–Asp) by integrin receptors. They use noncovalent interactions including salt bridges [5]. Vancomycin, a glycopeptide

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• -acetylnaphthyl group and a tetrapeptide (ᴅ-Phe–ᴅ-Phe–ᴅ-Lys–ᴅ-Tyr), and (iii) a glycine as the spacer for the incorporation of (i) and (ii). For the hydrophilic ʟ-peptide, DDD substitutes the XXX site in the DEXXXLLI sequence to increase the hydrophilicity of the peptides. In order to enable the self-assembly of

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• using shaped pulses that are specific for the respective side chain nitrogen atom (≈33 ppm for Lys Nζ and ≈85 ppm for Arg Nε). N-terminal glycine residues are also visible in the Lys-specific spectrum because the chemical shifts of the CαH2-NH3+ moiety also match the selected chemical shift range. Not

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• /ketones 33 with glycine derivatives 34 to synthesise the corresponding products 35 in good yields and excellent enantioselectivities (35 examples, up to 99:1 er) (Scheme 4b) [30]. The previous examples of enamine/photoredox catalysis have all required two or more separate catalysts. Currently, three

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• hydrophobic, while the introduction of a polar or an ionizable group makes it hydrophilic. Two amino acids stand out from the dualistic hydrophilic/hydrophobic classification: glycine and proline (Figure 1A) [1]. The origin of their effect onto the structure polarity is not due to the presence of additional

• ], organocatalysis [102], drug discovery [103] and more. A) Three types of the backbone amino acid structures that are included in protein translation: glycine, alanine, and the set of its structural derivatives, proline. B) The portfolio of the fluorinated amino acids developed to date. The set of amino acids

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• cyclized to form the desired phenanthridine 11.4 in excellent yield. Notably, the reaction could be readily applied to benzoimines having different substituents on the aromatic ring bearing the amino group [73]. Glycine derivatives having a biaryl group attached to the N-terminus were successfully

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• (Figure 3), by reaction of N-cinnamoylglycine (1) with the corresponding benzaldehyde ArCHO in acetic anhydride as solvent and in the presence of sodium acetate [42][43][44][45][46][47][48]. In turn, N-cinnamoylglycine (1) was prepared following the Schotten–Baumann method from glycine and cinnamoyl

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• -[18F]fluorophenylalanines 72a,b [54] were achieved by a copper-mediated nucleophilic radiofluorination of arylstannanes 71a,b with [18F]KF (Scheme 17). 1.6. Alkylation of benzophenone imine of glycine ester Pentafluoro-ʟ-phenylalanine (77a) and 2,4-ditrifluoromethyl-ʟ-phenylalanine (77b) were

• synthesized through alkylation of the benzophenone imine of glycine ester 73, with perfluorinated benzylbromide 19c or 2,4-bis(trifluoromethyl)benzyl bromide (74) in the presence of 2,7-bis[O(9)-allylhydrocinchonidinium-N-methyl]naphthalene dibromide, to afford the fluorinated phenylalanine imines 75a,b with

• 101c,d with modest enantiomeric excesses (33–66% ee) and in moderate yields [59] (Scheme 22). A convenient preparative method for the synthesis of enantiomerically pure o-, m-, and p- or pentafluorinated phenylalanines 53a, 81, 101c, and 107 was carried out by the alkylation of glycine. The Ni(II

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• compared to a benzyl substituent [18]. The deleterious effect of a substituent α to the amine was most pronounced in the case of alanine (product 13), as compared to glycine (product 2). However, this steric constraint could be largely overcome by the presence of a β-hydroxy group, as seen with serine

• within the NMR tube with a large excess of the amine, the relative rate constants were determined for a representative set of amines (Table 3). These results further highlight the dramatic rate enhancement brought on by substituent effects. Glycine reacted most swiftly, as the carboxylate anion likely

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• with a bromoalkyne (Scheme 24) [39]. The catalyst was selected using a combinatorial approach for the selection of the optimal catalyst structure. The product was isolated in an excellent 87% yield. In 2018, Wang, Xu, and co-workers described the reductive decarboxylative alkylation of glycine and

• glycine-containing peptides using an in situ-formed heteroleptic copper complex, [Cu(I)(dmp)(xantphos)]PF6 (Scheme 25) [40]. Under blue light irradiation, glycine esters were readily alkylated using NHP esters in the presence of DABCO as a base. A large panel of NHP esters was introduced to ethyl N

• -phenylglycine ester, and the alkylated products were obtained in good to excellent yields. In addition, various glycine derivatives were also alkylated in good yields. Finally, the authors demonstrated the synthetic interest of their methodology through the alkylation of di- and tripeptides. The authors studied

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• compound, with applications ranging from thickening agents (carboxymethyl cellulose, E466) [1][2], herbicides (2,4-dichlorophenoxyacetic acid), cosmetics (cocamidopropyl betaine), dyes (indigo vat dye) [3], to pharmaceuticals (ibuprofen, glycine, malonates) [4] (see Figure 1). Many reactions with

• monochloroacetic acid have been published. The production of basic building blocks like glycine [5] (>600 000 tons/year in China in 2015) and diethyl malonate from monochloroacetic acid show the value of this compound as a starting material. Many reactions with monochloroacetic acid, including the synthesis of

• glycine and diethyl malonate, are based on nucleophilic substitution of the chlorine [6][7][8][9][10]. In an attempt to find new synthetic applications of monochloroacetic acid we turned our attention to photoredox catalysis. We were inspired by the rebirth of visible light photoredox catalysis, induced

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• diastereoselectivities, and ees up to 86% [26]. Rearrangement of allyl esters of glycine derivatives gave under similar conditions amino acids with a quaternary stereocenter on the β-carbon with high yields and excellent diastereo- as well as enantioselectivity [5]. A reductive rearrangement of allyl esters of acrylic

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• relatively small structural changes to probe the biosynthetic machinery: the native sequence ᴅ-alanine-dehydroalanine-sarcosine was varied in a small library by replacing dehydroalanine (Dha) with ᴅ- or ʟ-alanine and sarcosine with glycine (Figure 3). The synthesis of these biosynthesis analogs 9–14 was

• performed following solution phase Boc-protected peptide coupling and functional group interconversion (Scheme 1). The central alanine carrying nonnatural derivatives were sequentially synthesized from C- to N-terminus, using ester protected glycine or sarcosine and coupling to Boc-protected ᴅ- or ʟ-alanine

• group gave the unnatural analogs containing ᴅ- or ʟ-alanine at the dehydroalanine site and sarcosine or glycine at the C-terminus (9–12) in generally acceptable yields. The synthesis of the dehydroalanine containing analogs 13 and 14 was performed following the same strategy with incorporation of a