Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• arbitrarily as we have frequently employed them to optimize mass spectrometric procedures. Also, we were interested to test, if threonine or tyrosine residues, respectively, would lead to better labeling efficiency. Because mannoside 3 is poorly water soluble, it was dissolved in methanol and then added to

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• several experiments, treatment with a catalytic amount of TMSOTf was found to be suitable for the intramolecular glycosylation, giving the corresponding acid, which was easily converted to the corresponding methyl ester 180 under EDCI/DMAP/MeOH conditions [85]. Similarly, the reaction of the threonine

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

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• a non-binding mutant of the target CTB protein [66], oxidised the N-terminal threonine residue of each subunit to an aldehyde and then chemically attached GM1os ligands by oxime ligation (Figure 15). This neoglycoprotein was able to display the five copies of the carbohydrate ligand with appropriate

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

• phenylalanine, tyrosine, tryptophan, and leucine in the P1 position. Secondary hydrolysis also occurs at the carbonyl end of isoleucine, methionine, serine, threonine, valine, histidine, glycine, and alanine [47][58][59][60]. The S2 subsite of α-chymotrypsin generally prefers to accommodate hydrophobic residues

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

• , L-threonine, (2S,3R)-L-CF3-threonine and (2S,3S)-L-CF3-threonine were prepared. The capacity of (2S,3S)- and (2S,3R)-CF3-threonine analogues to stabilize an extended structure when introduced in the central position of pentapeptides is demonstrated by NMR conformational studies and molecular

• dynamics simulations. CF3-threonine containing pentapeptides are more prone to mimic β-strands than their natural Ser and Thr pentapeptide analogues. The proof of concept that these fluorinated β-strand mimics are able to disrupt protein–protein interactions involving β-sheet structures is provided. The

• CF3-threonine containing pentapeptides interact with the amyloid peptide Aβ1-42 in order to reduce the protein–protein interactions mediating its aggregation process. Keywords: aggregation; beta-sheet; fluorine; peptide; unnatural amino acid; Introduction It is estimated that 20% of administered

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• protection. Xaa-ψ[CF=C]-Pro The first asymmetric synthesis of Xaa-ψ[CF=C]-Pro was reported in 2012 by Chang’s group with the synthesis of MeOCO-Val-ψ[(Z)-CF=C]-Pro 93 (Scheme 18) [52]. Their synthesis started with a stereoselective aldol reaction using (L)-threonine to furnish a chiral β-hydroxy

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• retaining mechanism). In the case of O-GTs, the nucleophile is an alcohol or a phenol (carbohydrates, serine, threonine, …), whereas in N-GTs, the nature of the nitrogen-containing group is more diverse (amines, amides, guanidine or even indoles) [12]. S- and C-GTs follow a similar mechanism with the

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• or L-(tert-butyl)threonine methyl esters, ureido derivatives 38 and 39 were isolated in high yields (96 and 97%, respectively; Scheme 16a,b). A number of other α-amino methyl esters, quaternary amino methyl esters or β-amino methyl esters were also successfully converted to intermediate ureas

• mechanochemical conditions. a) HOMO−1 contours of mono-thiourea 19b and mono-urea 36. b) Mechanochemical synthesis of hybrid urea-thioureas 37a–d. Synthesis of ureido derivatives 38 and 39 from KOCN and hydrochloride salts of a) L-phenylalanine methyl ester and b) L-threonine(Ot-Bu) methyl ester. c

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• different downstream signaling cascades. As the core component of these complexes, mTOR exhibits protein kinase activity and phosphorylates a variety of downstream meditators. One of the principal substrates of the mTORC2 complex is the serine/threonine kinase Akt, which gets activated upon phosphorylation

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• ; Introduction Fusaricidins are lipid-modified non-ribosomal cyclic hexadepsipeptides containing four D-amino acids and two L-amino acids. All of them carry an L-threonine linked to a unique 15-guanidino-3-hydroxypentadecanoic acid side chain through the N-terminus. This particular ω-functionalized lipid side

• alcohol 12 was subjected to ozonolysis and Pinnick oxidation to furnish the protected GHPD acid 3 in an overall yield of 14.3%. The peptide core was synthesized manually according to a standard SPPS Fmoc protocol using HATU and NMM in NMP [16]. For protection of the threonine unit, it was converted into a

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• molecular target of PMA was identified in a series of isoforms of PKC, a family of serine/threonine kinases involved in a host of cellular activities [9]. Because of its kinase-activating properties, PMA has become an indispensable tool in the study of cell function, with a single vendor claiming to have

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• (tRNAs) loaded with amino acids, which use a possibly degenerate RNA complementary code (using the triplets that form anticodons) to establish the correspondence between the codons and each of the 20 amino acids. Some triplets (for example, the four codons ACN code for threonine) are ambiguous, imposing

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• . GPCRs are normally deactivated by β-arrestin, as shown in Figure 4. After activation and dissociation of the β/γ subunit, IL3 and the C-terminus of the GPCR are phosphorylated at serine and threonine residues (Figure 4a). This phosphorylation allows the recruitment of β-arrestin (Figure 4b), which can

Solid-phase enrichment and analysis of electrophilic natural products

• Frank Wesche,
• Yue He and
• Helge B. Bode

Beilstein J. Org. Chem. 2017, 13, 405–409, doi:10.3762/bjoc.13.43

• namely glidobactin A (4) [22], cepafungin I (5) [23][24] and luminmycin D (6) [25][26] were enriched (Scheme 2). Glidobactins are well-known proteasome inhibitors that react with a conserved threonine residue in the β5 subunit of the proteasome [24]. From Photorhabdus strains they have previously only

• crude extract (Supporting Information File 1, Figure S10). The comparison of the MS/MS spectra of natural and azidated 4 revealed that the reaction took place at the ring-double bond that is also attacked by the threonine in the proteasome (Supporting Information File 1, Figure S11). To the best of our

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• has occurred at an internal tryptophan residue of the precursor peptide. Kawaguchipeptin A Apart from the ComX pheromones, post-translational dimethylallylations of the tyrosine, threonine, serine, and tryptophan residues of cyclic peptides from cyanobacteria were reported [49][50][51]. The RiPPs

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• have been exploited as valuable building blocks in natural product syntheses, e.g., calyculins A and B as potent serine-threonine protein phosphatase inhibitors [6], as well as ligands in enantioselective reactions [7]. Furthermore, allylphosphonates are important bioactive compounds that exhibit

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• cells [50]. The serine/threonine kinase PKA uses ATP as phosphate donor. It has to be activated from its natural species with cAMP which leads to dissociation of PKA in two regular and two catalytic subunits [51]. We used the preactivated catalytic subunit of PKA to perform the reactions. The structural

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• according to the procedures previously described in literature [14][23]. In order to obtain phosphoramidite 11 we have developed a synthesis (Scheme 2) based on L-threonine as a starting material. L-Threonine was converted to bromo-derivative 6 by a diazotization reaction using sodium nitrite followed by

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• -butanol (16), 5-azidopentanol (17), cyclohexanol (18) and 2-adamantanol (19), to give O-2-deoxyglucosides in high yields (74–90%) and α-selectivities (α:β = 7–10:1, Table 3, entries 2–8). Regarding the glycosylation with amino acid derivatives, L-serine 20 and threonine derivative 21, increased ratio of β

• -Serine and threonine derivatives 20 and 21 reacted with galactal 4 to give the glycosylated amino acids 59 and 60 (Table 4, entries 9 and 10) in excellent selectivities (59, α only; 60, α:β = 9:1) but in different yields (59, 50%; 60, 97%). In Table 4, entry 11, disaccharide 61 was acquired in the

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• crosslinks are formed via a two-stage process. Firstly, serine (for Lan) and threonine (for MeLan) residues are dehydrated to 2,3-didehydroalanine (Dha) and (Z)-2,3-didehydrobutyrine (Dhb), respectively (Figure 4B). This is followed by 1,4-nucleophilic additions onto these didehydro amino acids by cysteine

• actively transcribed thiopeptide gene clusters in human microbiota from every body site assessed [6]. Thiazoles in thiopeptides are introduced by a BCD-protein system described previously, while threonine and serine residues are dehydrated by lantibiotic-like dehydratases. The formation of core pyridine

• macrolactones form from the condensation of threonine or serine side chains with aspartate or glutamate side chains. Studies on microviridin B (Figure 7B) from Microcystis aeruginosa NIES298 and microviridin K from Planktothrix agardhii CYA126/8 demonstrated that one ligase is responsible for ester formation

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• Jaroslav Padevet Marcus G. Schrems Robin Scheil Andreas Pfaltz Department of Chemistry, University of Basel, St. Johanns-Ring 19, CH-4056 Basel, Switzerland 10.3762/bjoc.12.114 Abstract A synthesis of new NeoPHOX ligands derived from serine or threonine has been developed. The central

• the substantially higher ee values induced by the analogous catalyst Ir-1a [28] lacking substituents at C(5). Based on these negative results we chose a new approach based on serine or threonine as starting materials (Figure 4). The carboxyl group of these amino acids serves as surrogate for the tert

• protecting group, the steric properties of the ligand can be optimized for a specific application. PHOX ligands of this type have been previously prepared from serine and successfully used in iridium-catalyzed hydrogenation [29][30]. Synthesis of serine- and threonine-derived NeoPHOX ligands The synthesis

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• and threonine derivatives. Keywords: amino acids; olefination; protecting group free; synthetic methods; Wittig reactions; Introduction Allylic amines have received significant attention because they represent a common scaffold in diverse biologically relevant compounds and natural products [1]. In

• and threonine, additional O-protection and O-deprotection steps are required (Figure 1). Thus, Garner’s aldehyde [12][13] or N- and O-protected amino ester derivatives have been required [14]. All those methodologies involve long reaction sequences, including protection–deprotection and/or oxidation

• aldehydes. It comprises the one-pot sequential reduction to aldehyde with DIBAL-H at −78 °C and subsequent in situ addition of Grignard reagents. Remarkably, our method is friendly with serine and threonine derivatives without the requisite to protect the β-hydroxy group. With this tool in hand, we thought

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• -addition to allenoates, which after elaboration of the resulting adducts, affords tertiary thioethers and alcohols [36] (Scheme 15). Starting from readily available L-valine and L-threonine the authors first synthesized different phosphine catalysts and then screened in the γ-addition reaction of both