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

• entirely unreactive under the typical reaction conditions. In this case the reaction required 3 h at 130 °C before product formation was observed. Interestingly, much like the improved results for serine, a β-hydroxy group dramatically overcame this issue for secondary amines, as 2-(methylamino)ethanol

• ion pairs with the cationic DBU-activated acyl intermediate (see Figure 1). However, the α-substitution in alanine clearly abolishes any rate acceleration driven by ionic interactions, and most α-substituted amines had similar rates. Rate acceleration is recovered in serine, owing to the effect of the

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

• benzyl protected serine at the Dha site. Following hydrogenolytic deprotection, in situ produced serine EDC adduct was subjected to copper(I) chloride-mediated elimination to give the dehydroalanine derivatives 34a and 34b in good yields. Deprotection of the ester protecting group also proceeded in good

Isolation and biosynthesis of an unsaturated fatty acid with unusual methylation pattern from a coral-associated bacterium Microbulbifer sp.

• Amit Raj Sharma,
• Enjuro Harunari,
• Tao Zhou,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2327–2332, doi:10.3762/bjoc.15.225

• these organisms. C-Methylation at C9 of fungal sphingosines is similarly catalyzed by SAM-dependent methyltransferases [16]. The methylation takes place at the alkenyl carbon (C9) which is originally derived from the carbonyl carbon of an acetate unit: C1 and C2 of sphingosines are derived from ʟ-serine

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• could be prepared from ᴅ-mannitol. While derivatives of glyceraldehyde are configurationally stable Garner’s aldehyde 3a [8][9], available from ʟ-serine, is configurationally labile and samples with ee as low as 75% can be obtained depending on the reaction conditions. Significant improvement in terms

• by transforming enantiomerically pure (2R,1'S)-5a and (2S,1'S)-5a into (R)- and (S)-serine, respectively (Scheme 2) [13][16]. Synthesis of N-(1-phenylethyl)aziridine-2-carbaldehydes 6 Aziridine aldehydes 6 are in most instances prepared from the corresponding alcohols 7 by Swern oxidation [28][29][30

• )-5a was reacted with 3-bromo-5-methoxy-1H-1,2,4-triazole (128) to give N-protected bicyclic amino ester 129 which was next converted into (S)-(+)-127 in two standard steps (Scheme 33) [17]. Its enantiomer was prepared from (2R,1′S)-5a. Lacosamide ((R)-130) is a derivative of ᴅ-serine and has found

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• the serine residue and the amide proton of GalNAc unit [33]. This correlates with our results obtained for longer peptides containing the same sugar moiety attached to threonine. Moreover, Corzana et al. [33] highlighted the importance of surrounding solvent molecules, which are responsible for the

• determined, no predominant conformer was found. As shown in Figure 3A and B both tripeptides indicate a fully flexible conformation. Corzana et al. suggested for the C- and N-protected, glycosylated ʟ-serine residue an extended conformation without intramolecular hydrogen bond between the amide proton of

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• Scheme 4, the authors developed methods for the functionalization of spirostanic steroids and their further conjugation to amino acids by means of the Ugi-4CR. Thus, seco-steroidal amine 10 – derived from the steroidal sapogenin hecogenin (9) – was ligated to Boc-protected serine in presence of

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• cytotoxic agent. The problem of concomitant toxicity to healthy cells has been circumvented by attaching a short peptide (His-Ser-Ser-Lys-Leu-Gln-Leu) to a tether at TG’s C-8 position (1b). This modification renders the inhibitor inactive [3]. Prostate cancer cells produce on their surface the serine

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• described as a potent inhibitor of various proteases, in particular trypsin and thrombin [17][18][19]. Hereby, the α-keto amide covalently binds to the serine oxygen in the active site under formation of a stable tetrahedral hemiketal. Furthermore, substitution of the indole hydrogen by alkyl, aryl or

• , the azaindole derivatives are currently under investigation upon their use for fluorescence imaging. Furthermore, derivatives 3 and 6 will be further studied for identification of their actual target in S. aureus. This could be a serine protease that can also be addressed in the future by more stable

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• [70]. α-Chymotrypsin is a serine protease that recognizes hydrophobic residues in one of its clefts. A modified HG-type catalyst (66) contains an L-phenyl chloromethyl ketone moiety that acts as inhibitor and is first recognized by supramolecular anchoring and then covalently attaches upon

• , entries 2, 7 and 12). Gebbink and co-workers anchored the HG-type catalyst 79 to cutinase, a serine hydrolase [75]. The phosphonate ester moiety acts as a suicide inhibitor forming an irreversible covalent bond to a serine residue present in the active site of the enzyme. Assembly of ArM 8 occurs at pH 5

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• ) derivatives and dipeptides. In this regard, trimerization and Negishi cross-coupling reactions are used as the key steps starting from readily available 4’-iodoacetophenone and L-serine. These C3-symmetric molecules containing AAA moieties are useful to design new ligands suitable for asymmetric synthesis and

• . Results and Discussion The required zinc insertion compound 7 was prepared from L-serine (3). Thus, commercially available L-serine (3) was treated with acetyl chloride in methanol to give methyl ester 4, which was subjected to N-Boc protection with di-tert-butyl dicarbonate (Boc2O) and triethylamine in

• tetrahydrofuran (THF) to obtain the N-Boc-serine methyl ester (5) in 93% yield [42]. Afterwards, the protected methyl ester 5 was subjected to iodination in the presence of iodine (I2), triphenylphosphane (PPh3) and imidazole in CH2Cl2 at 0 °C to deliver the iodo derivative 6 in 63% yield [43][44]. Finally, the

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• obtained under controlled reaction conditions, clearly indicated that one amino group (Dab) and three OH groups are present in the toxin. As shown in Table 1, cichorinotoxin has three OH groups in its structure due to the presence of two serine residues and one threonine residue. In addition, one 3

• -hydroxyfatty acid is present, as described above (Figure 2). Thus, there are four OH groups in cichorinotoxin. As mentioned below, the four acetate moieties were determined to be at Dab, the two serine residues and the β-hydroxyfatty acid based on NMR analyses. Thus, the OH group on the Thr residue is blocked

• , is acetylated. The tetraacetate (4), in which the fatty acid, two serine residues (Ser12 and Ser21) and Dab20 are all acylated, had no activity. Ser12, which is present in the linear portion of the peptide, is not conserved in the toxins listed in Supporting Information File 1, Figure S15; thus, it

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• groups capable for the formation of additional hydrogen bonds, both as donors and acceptors. The majority of synthetic strategies starts from natural products and relies on application of chirons having the required configuration at the carbon atom bonded to nitrogen (e.g., serine, glutamic and

• of Subtilisin Carlsberg to give dibenzyl (2R,3S)-N-Boc-3-hydroxyglutamate and (2S,3R)-5-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-oxopentanoic acid [25]. The majority of asymmetric syntheses of 3-hydroxyglutamic acid employ serine or similar three-carbon chirons as starting materials

• . Configuration at Cα is retained in the final products and it also induces chirality at the Cβ(OH) center. The hydroxymethyl group of serine can serve as a precursor of the carboxyl fragment but when oxidized to aldehyde it may be attacked by nucleophiles to introduce the required two-carbon residue. From serine

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• modifications of glycocalyx proteins are N-glycans (asparagine-linked) and O-glycans (serine- or threonine-linked), while glycosphingolipids are the major subclass of glycosylated lipids in the cell membrane of human cells (Figure 2). While many core elements of glycocalyx oligosaccharides are conserved between

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• compatibility is of immense versatility since synthesized peptide fragments, which are cleaved from their supports thus freeing the C-terminus, could directly be conjugated to the 5’-terminus of oligonucleotides via tyrosine, serine, or threonine side chains. In order to demonstrate such a versatile conjugation

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• ]. Compared with classical solution-phase peptide synthesis, the fast development of SPPS is mainly due to its short reaction time, high efficiency, low racemization, simple work-up and automation. In recent decades, various strategies, for example, native chemical ligation (NCL) [32] and serine/threonine

• moderate yield (Table 1, entries 3 and 4). Notably, it is unnecessary to protect the hydroxy group of serine, threonine, or tyrosine in advance in the synthesis of these four peptides. The presence of an unprotected hydroxy group does not affect the coupling efficiency, which is consistent with peptide

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• , glycoproteins serve as ligands for specific extracellular recognition processes toward, e.g., enzymes, lectins or antibodies [2]. In O-linked glycoproteins, also known as mucins, GalNAc becomes covalently α-linked to serine or threonine during post-translational modifications [3][4][5]. This glycoconjugate

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• . Furthermore, the incorporation of an acetylated lysine instead of the native serine in position 4 decelerated the degradation by α-chymotrypsin which catalyzed the hydrolysis of the peptide bond exclusively between 3Trp and 4Aaa. A similar effect was observed for GnRH-III conjugates in which the ε-amino group

• of 4Lys was acylated by different SCFAs. It is worth to mention that the main cleavage sites of GnRH peptides by different enzymes are at both sides of serine in position 4 [39][40], that can be prohibited by replacement of Ser with an acylated lysine. Moreover, it has been shown that the stability

• that contain 4Lys(Bu) (K2, 4–6) instead of serine indicate a proteolytic cleavage by lysosomal endopeptidases, which might be of great importance for the release of the smallest Dau-containing metabolite. Cytostatic effect of the bioconjugates Cell lines often function as the first model system of

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• green catalysis. Peptide dendrimers including aspartate, histidine and serine were utilized by Reymond et al. as catalytic esterase triad. Using fluorogenic 8-acyloxypyrene-1,3,6-trisulfonates as substrate (Figure 7) at the pH optimum of 5.5, triads’ activity was successfully demonstrated [107]. A

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• such intermediates. By selecting the appropriate reaction conditions (various pH and temperatures), they were able to alkylate free amino acids, e.g., glycine (Gly), L-serine (Ser), L-cysteine (Cys), L-lysine (Lys), L-tyrosine (Tyr) and glutathione (Glu) in aqueous solution to isolate 55 (Scheme 8

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• -like-peptide-1 (GLP-1), which is an attractive lead compound for the treatment of diabetes mellitus type 2. Unfortunately, the clinical use of the wild-type peptide is severely hampered due to rapid digestion (≈2 min) by the serine protease dipeptidyl peptidase [24][25][26]. Satisfyingly, the

• site and the particular protease [39][40]. Here, we extend these studies to include highly fluorinated, sterically demanding HfLeu, and 5,5,5-trifluoroisoleucine (TfIle) and to investigate their effects on proteolytic stability towards the serine proteases α-chymotrypsin, elastase, and proteinase K

• detailed description of the results for the individual enzymes is given in the following sections. Proteolytic stability towards α-chymotrypsin (EC 3.4.21.1) α-Chymotrypsin is a serine endopeptidase with broad specificity. It preferably cleaves peptide bonds C-terminal to large hydrophobic residues such as

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• Sorbonne Universités, UPMC Univ Paris 06, Ecole Normale Supérieure, PSL Research University, CNRS, Laboratoire des Biomolécules, 4 place Jussieu, 75252 Paris Cedex 05, France 10.3762/bjoc.13.276 Abstract Pentapeptides having the sequence R-HN-Ala-Val-X-Val-Leu-OMe, where the central residue X is L-serine

• proteins aggregation characterized by ordered β-sheet structure assemblies [14][15]. In this context, we synthesized and analyzed, by NMR and molecular modeling, the conformational preferences of eight pentapeptides, containing a L-serine, a L-threonine, a (2S,3R)-L-allo-CF3-threonine or a (2S,3S)-L-CF3

• that the presence of fluorine atoms probably increased the interaction of pentapeptides with Aβ1-42 and their inhibitory effect on Aβ1-42 aggregation. Conclusion We synthesized eight pentapeptides 1a–4a and 1b–4b having the sequence RHN-Ala-Val-X-Val-Leu-OMe, where the central residue X is L-serine, L

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• fluorescence push–pull system would be destroyed. To confirm this, we modified 1 to provide a peptidic substrate for an enzyme. The serine protease DPP-4 was used as the test enzyme because its substrate specificity is clear: it hydrolyses the C-terminal of proline or alanine second to the N-terminal of the

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• propargylamines without an acidifying Cα-substituent. Synthesis of propargylamines containing polar or acidic functional groups The synthesis of propargylamines with polar substituents to mimic polar amino acids such as serine (alcohol), cysteine (thiol) or glutamine (carboxamide) requires special protective

• was successfully applied as protective group to obtain the homologated serine analogous propargylamine 7t similar to the description by Verrier et al. [47][55], starting from TBDMS-protected oxybutanal. Treatment of alkyne 6t with TBAF leads to simultaneous cleavage of both silyl groups. Although

• sterically shielding protective groups have proven convenient, the trityl group turned out to be inefficient to generate a serine-analogous propargylamine. Trityl-protected imine 5m immediately decomposed, when treated with (trimethylsilyl)ethynyllithium. The preparation of glutamic acid-analogous

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• = 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, DPPS = 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine, DPPA = 1,2-dipalmitoyl-sn-glycerol 3-phosphate. Chirally 2H-labelled tripalmitins (1S)- and (1R)-1-[2H]-1 [23]. 1H NMR data and helical conformational properties of tripalmitin 1 and 3-O-benzyl