The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• bond formation (path A), as postulated by Griesbeck et al. for the photocyclization of phthaloyl-L-methionine [58]. Alternatively, the alcoholate obtained after C–C bond formation may cyclize to the oxazolidine (path B), as known from reactions of 1a with organometallic reagents [48][49][50]. When

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• responsible guanylyltransferase uses GTP as substrate and forms a covalent enzyme-(lysyl-N)-GMP intermediate, reminiscent of DNA ligase-AMP intermediates [30][31]. Finally, the cap structure is methylated at the N7-position by an RNA(guanine-N7)methyltransferase using S-adenoysl-L-methionine (AdoMet) as a

• . Enzymatic modification is based on methyltransferases which naturally transfer a methyl group from their cosubstrate S-adenosyl-L-methionine (AdoMet) to the target molecule [85]. Functionalized side chains can be transferred from AdoMet analogues if an appropriate promiscuous methyltransferase is available

• double labeling of the mRNA cap with alkyne moieties could also be achieved based on a recently reported enzymatic cascade reaction [99]. In this system a Se-propargyl-modified AdoMet analogue (SeAdoYn [100]) was prepared enzymatically from the respective methionine analogue and ATP by a methionine

Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts

• Jan Wallbaum and
• Daniel B. Werz

Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254

• change in selectivity was observed while using electron-withdrawing methyl amide 9d; the influence of the para-nitro substituent decreases the yield of the desired cis-diastereomer to only 12%. Utilization of non-aromatic methyl amides 9e and 9f, synthesized from L-norvaline and L-methionine methyl

• ; found, 291.1468. (2S,5S)-3-Methyl-5-(2-(methylthio)ethyl)-2-(naphthalen-1-yl)imidazolidin-4-one (7g). (S)-Methionine methyl amide (649 mg, 4.00 µmol, 1.0 equiv), 1-naphthyl carbaldehyde (562 mg, 489 µL, 3.60 mmol, 0.9 equiv), 4 Å molecular sieves (480 mg) and Yb(OTf)3 (248 mg, 400 µmol, 10 mol %) in THF

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

• Kohei Yamada,
• Naoto Kamimura and
• Munetaka Kunishima

Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146

• substitution pattern at the 4-position of the oxazole. The one-pot oxazole synthesis with phenylalanine (2b), valine (2c), leucine (2d), methionine (2e), and phenylglycine (2f) proceeded to give the corresponding intermediates in good yields (Table 1, entries 6–10). Despite the existence of highly polar

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

Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates

• Tyler M. M. Stack,
• William H. Johnson Jr. and
• Christian P. Whitman

Beilstein J. Org. Chem. 2017, 13, 1022–1031, doi:10.3762/bjoc.13.101

• -terminal methionine, the same enzyme with an N-formylmethionine, the intact enzyme with an N-terminal methionine, and the intact enzyme with an N-formylmethionine [25]. Synthesis of ethyl 2-fluorocrotonate and ethyl 2-bromocrotonate Ethyl 2-fluorocrotonate was synthesized following published procedures [18

Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and ³J_HH coupling constant analyses

• Weslley G. D. P. Silva,
• Carolyne B. Braga and
• Roberto Rittner

Beilstein J. Org. Chem. 2017, 13, 925–937, doi:10.3762/bjoc.13.94

• conformational analysis of esterified and N-acetylated derivatives of L-methionine and L-cysteine using a combination of 1H NMR and electronic structure calculations is reported. The geometries and energies of the most stable conformers in isolated phase and taking into account the implicit solvent effects

• analysis; cysteine; methionine; NMR spectroscopy; quantum chemical calculations; Introduction Amino acids constitute the building blocks of proteins and peptides, which play an important role in numerous biological processes [1][2]. However, their studies in both isolated and condensed phases have been

• been more widely reported, mainly in gas phase [3][4][5][6][7][8]. Among the 20 amino acids incorporated into proteins, L-methionine (L-Met) and L-cysteine (L-Cys) are the only two containing sulfur. The former is an initiator amino acid in the protein synthesis of all eukaryotics cells [9], whereas

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• naturally leads to the formation of tricyclic taxadiene [56] was achieved by exchanging a valin in position 584 with methionine. The resulting product was identified as a bicyclic diterpene of the verticillene type [51] (Scheme 2). A single residue switch in position 753 (W753H) presumably causes premature

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• valine and its C-methylation with methionine and the polyol carbons are derived from a glycolysis intermediate, possibly hydroxymalonyl-ACP. Keywords: biosynthesis; butyrolactol; contiguous polyol; hydroxymalonyl-ACP; polyketide; Streptomyces; tert-butyl; Introduction Actinomycetes produce structurally

• likely supplied through the C-methylation of valine. To examine this possibility, feeding experiments of L-[methyl-13C]methionine and L-valine-d8 were carried out. As expected, the tert-butylmethyl carbons (C-25, C-26, C-27) were labeled as a result of L-[methyl-13C]methionine incorporation (Table 1). In

• deuterium atoms into the terminal methyl groups. Based on these results from precursor-feeding experiments, we concluded that the tert-butyl group and the adjacent methylene carbon (C-23) are derived from valine and the S-methyl carbon of methionine. It is controversial whether pivaloyl CoA is loaded onto

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• positionally undefined heavy atoms obtained after an unspecific ligand-soaking procedure, new methods were developed. One highly defined method is to directly substitute methionine by selenomethionine in recombinantly expressed proteins [19][20]. On the other hand, the co-crystallization of a protein in

• was available for molecular replacement and the protein contains only one methionine and no cysteine residues, which is insufficient to consider incorporation of selenomethionine in the protein for the structure elucidation. Its carbohydrate-binding specificity was determined and a preference for O

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• ., alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, cysteine and methionine), they can be easily included inside the CDs. This complexation leads to modification of the protein. For sake of clarity, only some typical examples are reported in this section. In their paper on the

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• mechanism is reminiscent of the formation of a tetrahydropyridine ring by the berberine bridge enzyme in plant alkaloid biosynthesis. It starts with S-adenosyl-L-methionine (SAM)-dependent methylation of the secondary hydroxy group in 81 by the O-methyltransferase Leu14 (Scheme 14a) [71][72][73][74

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• either methionine for mureidomycins, napsamycins and sansanmycins or alanine in case of pacidamycins. Remarkably, these natural products share a urea peptide motif with the muraymycins. They are mainly active against Gram-negative bacteria, which is a noteworthy difference to the muraymycins and other

• central leucine unit and the terminal truncation had no crucial effects on the antibacterial activity (Table 2). Truncated derivatives 92f–h (Figure 10) without the L-valine urea terminus contained L-ornithine (L-Orn, 92f), L-arginine (L-Arg, 92g) and L-methionine (L-Met, 92h), respectively. They were

• give uridine-5'-aldehyde 99. Aldehyde 99 then supposedly undergoes an aldol addition with glycine 100 as the enol(ate) component, thus furnishing the amino acid–nucleoside hybrid 5'-C-glycyluridine (GlyU, 101). Alkylation of the 6'-amino group is then achieved by reaction with S-adenosyl methionine

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• biosynthesis was investigated using various 13C-labeled precursors [55]. Hence, it was concluded that beside four acetate units also two propionate units and one butyrate unit form the backbone, while the O-methylation is S-adenosyl-methionine dependent. Also cyclooxygenase-2 (COX-2) inhibitors are an

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• branched polyketides at the α-position of the growing chain include the usage of different elongation units such as methylmalonyl-CoA, or methylation of the nucleophilic α-position by S-adenosyl methionine (SAM) [21]. Branching in the β-position is less common and proceeds through a β-aldol attack of an

• experiments are rare, but can provide interesting insights into the biosynthesis of sulfur containing natural products. Besides the recently presented synthetic developments towards 36S-labeled SAM and methionine [77], also [34S]cysteine has been made accessible by synthesis from elemental 34S8 and used to

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• canonical amino acids, particularly cysteine. For example, SPI was used to introduce a NCAA such as azidohomoalanine (Aha) in a methionine-(Met)-auxotroph in combination with the chemical modification of the natural amino acid cysteine [30][31]. These handles were, e.g., addressed by CuAAC and disulfide

• amino acids like glycine, alanine or serine in the native process of N-terminal methionine excision (NME) [43]. This process exposes Ser2 at the N-terminus for subsequent N-terminal oxime ligation. It has to be noted that the incorporation of Aha, as known [42][44], can hamper NME and therefore delivers

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• another study Chen and co-workers found a GLP-1R antagonist only because of an unexpected dimerization [5]; and a dimer of S-adenosylmethionine is up to 13-fold more active than the monomer for promoting the binding of Escherichia coli methionine repressor to its operator DNA [6]. Peptoids are compounds

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• ) was prepared as previously described by reaction of (S)-methionine with bromoacetic acid [25]. Reaction of homoserine lactone hydrobromide (1) with the corresponding acid chloride 2 under Schotten–Baumann conditions gave the desired N-acylated homoserine lactones 3a–f (Scheme 1) [26]. These reaction

• mixture of (S)-methionine (15.2 g; 0.10 mol) and bromoacetic acid (1.1 equiv, 15.4 g, 0.11 mol) in 150 mL of a H2O–iPrOH–AcOH mixture (5:5:2 v:v:v) was stirred under reflux overnight. The solvent was then removed under reduced pressure. Subsequently, the orange sticky oil was partly dissolved in 50 mL of

Photo, thermal and chemical degradation of riboflavin

• Muhammad Ali Sheraz,
• Sadia Hafeez Kazi,
• Sofia Ahmed,
• Zubair Anwar and
• Iqbal Ahmad

Beilstein J. Org. Chem. 2014, 10, 1999–2012, doi:10.3762/bjoc.10.208

• greatest stabilizing effect by disodium ethylenediamine (EDTA) (96.2%), followed by thiourea (88.2%), methylparaben (86.4%), DL-methionine (76.3%), sodium thiosulfate (72.9%), ribonucleic acid (59.3%) and reduced glutathione (26.2%). When RF solutions were exposed to a 40 W fluorescent light (Sylvania

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• from methionine and studies towards the preparation of glutamic and aspartic acid derived heterocycles are presented. Following the retrosynthetic analysis in Figure 2 the relative configuration of B (cis/trans) should be controlled through targeted protecting group (PG) manipulation: Reduction of the

• , phenylalanine, phenylglycine and methionine 1a–d were converted to their N-benzyl-N-carbamate-protected derivatives 2a–d (PG = Cbz, Boc) in a practical one pot procedure through combination of Quitt´s reductive benzylation protocol [61] and a Schotten–Baumann acylation [62][63] in 70–95% yield (Scheme 1). While

• we choose a Cbz protecting group for the amino acids 1a–c due to the mild cleavage conditions (hydrogenolysis), we decided to introduce a Boc group at the N-terminus of methionine 1d to avoid desulfuration (–EtSMe → –Et) in the later deprotection. In order to suppress the formation of the only

Multicomponent reactions II

• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 115–116, doi:10.3762/bjoc.10.7

• been around in organic chemistry since the very early days. Indeed, the first example known in literature, the Strecker synthesis of α-aminonitriles [2], has been developed into an industrial process for the production of methionine in an annual scale of several hundreds of thousand tons per year. In

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• originates from glucose and methionine [23]. In 1996, Steglich isolated lycogalic acid A (38), also known as chromopyrolic acid, along with staurosporinone (30) and traces of arcyriaflavin A (31) from the extracts of Lycogala epidendrum [24]. This finding and results from Hoshino, which demonstrated that 38

• ) units. The remaining methyl groups are believed to be installed by S-adenosyl methionine (SAM). An intramolecular Aldol condensation generates the pyrrolinone 62, which reacts via an [4 + 2]-cycloaddition to prochaetoglobosin I (63) [56]. Recently, gene disruption studies of Chaetomium globosum revealed

Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe

• Matthew B. Plutschack,
• D. Tyler McQuade,
• Giulio Valenti and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 2022–2027, doi:10.3762/bjoc.9.238

• , methionine and histidine. As expected, the amino acids lacking functionality known to quench fluorophores (alanine, glutamine and lysine) did not quench NBDM at concentrations as high as 50 mM. Interestingly, tyrosine did not quench NBDM fluorescence even at concentrations as high as 2 mM (solubility limit

• for tyrosine). Methionine and histidine, however, did quench NBDM via a dynamic mechanism (Figure 4). Carbohydrate–carbohydrate and carbohydrate–aromatic ring interactions are well-known [29][30]. Based on these interactions, we hypothesized that abnormal fluorescence behavior may be exhibited at high

• fitted using a polynomial fit (order = 2) with direct weighting. Comparison of quenching 2 µM NBDM, as measured by fluorescence intensity of methionine and histidine. Each data set was plotted in OriginPro 8.6 and fitted using a linear fit with direct weighting. Batch synthesis of NBDM. a) NaNO2

Isotopically labeled sulfur compounds and synthetic selenium and tellurium analogues to study sulfur metabolism in marine bacteria

• Nelson L. Brock,
• Christian A. Citron,
• Claudia Zell,
• Martine Berger,
• Irene Wagner-Döbler,
• Jörn Petersen,
• Thorsten Brinkhoff,
• Meinhard Simon and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 942–950, doi:10.3762/bjoc.9.108

• further corroborated the proposed second demethylation activity in R. pomeroyi. Isotopically labeled [2H3]methionine and 34SO42−, synthesized from elemental 34S8, were tested to identify alternative sulfur sources besides DMSP for the MeSH production in P. gallaeciensis. Methionine proved to be a viable

• genome only encodes DddP as a single DMSP lyase, while no conclusions can be drawn on the participation of DddW. Exploring the source of methanethiol Two possible sources for MeSH production from MB2216 medium are sulfate via reduction to sulfide and methylation, or methionine via γ-lysis. The

• participation of both mechanisms was explored by feeding of isotopically labeled sulfate, thiosulfate and methionine. The volatiles released by agar-plate cultures of P. gallaeciensis fed with NaH34SO4 or Na34SSO3, both synthesized from elemental 34S8 (Scheme 3), were collected by using a CLSA and analyzed by

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• tryptic peptide S264-R281 from mouse cathepsin B, identified in pull-down experiments employing compound 9 in C2C12 cells. Observed sequence ions are labeled (m = oxidized methionine). In vitro biochemical and cellular activities of test compounds and controls. (n.a. = not active (cruzain IC50 > 50 μM