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

Skeletocutins M–Q: biologically active compounds from the fruiting bodies of the basidiomycete Skeletocutis sp. collected in Africa

• Tian Cheng,
• Clara Chepkirui,
• Cony Decock,
• Josphat C. Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2782–2789, doi:10.3762/bjoc.15.270

• cold 0.2 M glycine buffer at pH 10.5 was added. The amount of hydrolyzed 7-amino-4-methylcoumarin (AMC) was measured in a Tecan Infinite M200 PRO fluorescence spectrophotometer (excitation and emission at λ = 365 and 440 nm, respectively). Bestatin [12] and DMSO were used as positive and negative

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• diastereoselective Michael addition reactions [103][104]. The glycine–nickel complex 184 was deprotonated using a radical anion generated from the electrochemical reduction of azobenzene. The anionic Ni complex 185 acted as a good C-nucleophile towards Michael acceptors 186 resulting in diastereoisomeric mixtures of

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• -penetrating wavelengths. Peptide nucleic acids (PNAs) [31] are synthetic nucleic acid analogues, in which nucleobases are linked to a repeating N-(2-aminoethyl)glycine polyamide backbone. The lack of phosphate groups provides them with both higher binding affinities to complementary DNA or RNA sequences and

• )aminoethyl]glycine residue –Aeg(Alloc)– was selectively deprotected in the presence of Pd(OAc)2, Ph3P, NMM, PhSiH3 in CH2Cl2 for 2 h. Subsequently, carboxy photoswitches were introduced using Oxyma and N,N’-diisopropylcarbodiimide (DIC) as coupling agent. We explored two different types of photoswitches

• . Black lines controls: solid: FAM-ssDNA without PNA and under the same conditions; dashed: BHQ/FAM-dsDNA. Solid-phase synthesis of photoswitchable PNAs; Aeg = N-(2-aminoethyl)glycine, Bhoc = benzhydryloxycarbonyl. Isomerization conversions at the photostationary state (PSS). Melting temperatures (TM) of

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• diterpene synthases. Hence, the discovery of this novel motif might help in the identification and functional assignment of novel TPSs. The importance of the tryptophan residue in the WXXXXXRY motif of CotB2 was proven by mutation to glycine (W288G), where the product was changed to 3,7,18-dolabellatriene

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• synthesized and biologically evaluated [19][20][21]. The best adjuvant activity in experiments in vivo showed the ManAdTP derivative (Figure 2) which has a ᴅ-configuration at the (adamant-1-yl)glycine moiety and (R)-configuration at the hydroxyisobutyryl linker. Its activity was higher than PGM that was used

• racemic Boc-protected (adamant-1-yl)glycine [32] 2 using the carbodiimide EDC/HOBt method [21]. The obtained mixture of BocAdGly-ʟ-Ala-ᴅ-isoGlnOBn diastereoisomers was treated with trifluoroacetic acid in order to remove the Boc protecting group while the diastereoisomer 4 with ᴅ-ʟ-ᴅ amino acid sequence

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• , norheroin (1, Figure 3). Thus, norheroin (1) was synthesized according to literature procedure and purified by recrystallization [16]. Alkylation of 1 with tert-butyl bromoacetate and subsequent deprotection with trifluoroacetic acid yielded the N-glycine derivative of norheroin, 16. This critical

• corresponding alkene resulted in a mixture of products. We opted to try the synthesis of HF-2 by 1,4-addition, rather than reductive amination. Thus, intermediate 5 was acylated with acryloyl chloride to give the α,β-unsaturated intermediate 10 (Scheme 1). Condensation with a tert-butyl-protected glycine

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• and Constabel [17] who developed a solid phase strategy to obtain tetrazoles and hydantoinimide derivatives successfully (Scheme 2). In each case, the synthetic sequence began with a classical Ugi reaction between N-Fmoc glycine (1), isobutyraldehyde (2) and tert-butyl isocyanide (4) in the presence

• reactions in the synthesis of macrocycles (which were considered as macroheterocycles in the context of this review). In this respect, Wessjohann et al. developed a methodology for the synthesis of cyclic RGD pentapeptoids (RGD = arginine-glycine-aspartic acid) by consecutive Ugi reactions [32]. This was

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• nicotinic acetylcholine receptors (nAChRs), γ-aminobutyric acid type A receptors (GABAARs), and glycine receptors (GlyRs). To date, five subunits of the 5-HT3 receptor are identified (5-HT3A–5-HT3E) [21]. Functional receptors are either constructed as 5-HT3A homopentamers or as heteropentamers containing 5