Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• relationship to massiliachelin. Results and Discussion Massilia sp. NR 4-1 was cultivated in modified R2A medium under iron-replete conditions. As opposed to our former study [18], sodium pyruvate was not included in the medium, as this ingredient had been observed to enhance the production of violacein

• (Supporting Information File 1, Figure S1). In the absence of sodium pyruvate, the identification and isolation of minor metabolites from Massilia sp. NR 4-1 is facilitated, as already observed in the discovery of massinidine [17]. In the present study, several batch fermentations with a total culture volume

Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions

• Michael Keppler,
• Sandra Moser,
• Henning J. Jessen,
• Christoph Held and
• Jennifer N. Andexer

Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134

• substrate/product ratio is an important parameter for kinetics and for the reaction equilibrium, as it defines how much conversion will be achieved [25]. For acetate kinase a conversion of at least 90% using stoichiometric amounts of ADP and acetylphosphate was reported [26]. The reaction of pyruvate kinase

• mechanism exemplarily shown for the associative reaction pathway. a) Kinases as ATP regeneration enzymes, exemplified by the hexokinase-catalysed ATP-dependent phosphorylation of glucose. The ADP formed is converted back to ATP by pyruvate kinase using phosphoenol pyruvate as the phosphate donor [37]. b

• `-monophosphate (5F-UMP). The phosphorylation of the NMP is catalysed by the ATP dependent nucleoside monophosphate kinase yielding a 5F-UDP and ADP. 5F-UDP is then phosphorylated by pyruvate kinase under consumption of phosphoenol pyruvate [42]. c) Ranking of different phosphate donors that can be used for ATP

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• (−)-irofulven (87), Movassaghi et al. used a CuII-catalyzed asymmetric aldol reaction of O-silyl ketene S,O-acetal 84 with methyl pyruvate (85) to enantioselectively install the crucial tertiary TMS-protected alcohol in ester 86 (Scheme 14) [29]. Eleven further steps gave (−)-irofulven (87). 2. Mesoxalic

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• includes eight steps starting from the condensation of pyruvate and ᴅ-glyceraldehyde 3-phosphate (G3P) [13][14] (Figure 1a). Due to these lengthy biosynthetic steps as well as complex metabolic regulations and extensive cofactor requirements, several groups have engineered elegant bypass pathways to

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• the position of the reaction equilibrium. By this, equilibrium conversion, selectivity, and yield were increased from 57.9% to 63.9%, 81.9% to 84.7%, and 47.5% to 54.1%, respectively. This indicates a reduction in molar volume from N-acetyl-ᴅ-glucosamine (GlcNAc) and pyruvate (Pyr) to Neu5Ac. In

• particular, the circular reactor showed great potential to study reactions at high pressure while allowing for easy sampling. Additionally, an increase in affinity of pyruvate towards both tested enzymes was observed when high pressure was applied, as evidenced by a decrease of KI for the epimerase and KM

• for the aldolase from 108 to 42 mM and 91 to 37 mM, respectively. Keywords: aldolase; continuous fixed-bed reactor; enzyme; epimerase; GlcNAc; high pressure; immobilization; ManNAc; Neu5Ac; pyruvate; Introduction In times of a pandemic, the importance of substances to enhance the human immune system

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• -(trifluoromethyl)-9H-fluorenes, compounds containing a 9-(trifluoromethyl)-9H-fluoren-9‑ol partial structure can be found in the patent literature [33][34][35], where they have been claimed for their pyruvate dehydrogenase kinase (PDHK) inhibitory activity. The remarkable dienophilic reactivity of 1-CF3

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

• -difluorophenylalanine 115. Synthesis of β-fluorophenylalanine via 2-amino-1,3-diol derivatives. Synthesis of β-fluorophenylalanine derivatives via the oxazolidinone chiral auxiliary 122. Synthesis of β-fluorophenylalanine from pyruvate hemiketal 130. Synthesis of β-fluorophenylalanine (136) via fluorination of β

• -hydroxyphenylalanine (137). Synthesis of β-fluorophenylalanine from aziridine derivatives. Synthesis of β-fluorophenylalanine 136 via direct fluorination of pyruvate esters. Synthesis of β-fluorophenylalanine via fluorination of ethyl 3-phenylpyruvate enol using DAST. Synthesis of β-fluorophenylalanine derivatives

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• OH group in the tetrahydropyrimidine moiety (e.g., Scheme 2, VI and VIII), the formation of heterocycles that are amino-substituted in a similar position is also possible and has been described [31][32]. In particular, the reaction of methyl pyruvate and anilines led to the formation of 4-arylamino

• and pyruvic acid (3a) in acetic acid at room temperature under ultrasonication for 90 min gave 3-cyano-7-((4-cyano-1H-pyrazol-5-yl)amino)-5-aryl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-7-carboxylic acids 4a–c. There is also the possibility of applying ethyl pyruvate (3b) instead of pyruvic acid as

• (Figure 3). Conclusion In this study we disclosed a new direction for the multicomponent reaction of 5-aminopyrazole-4-carbonitriles or 3-amino-1,2,4-triazole with pyruvic acid or ethyl pyruvate and aromatic aldehydes under ultrasonication, leading to 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• KCl, 1.25 NaH2PO4, 7 MgCl2, 0.5 CaCl2, 26 NaHCO3, 10 glucose, 100 sucrose, 3 sodium pyruvate, 1.3 sodium ascorbate equilibrated with 95% O2/5% CO2 (pH 7.3–7.4). The brain slices were then incubated for 15 min at 33 °C in artificial cerebrospinal fluid (ACSF, mM: 125 NaCl, 2.5 KCl, 1.25 NaH2PO4, 1

• MgCl2, 2 CaCl2, 26 NaHCO3, 10 glucose, 3 sodium pyruvate, 1.3 sodium ascorbate; 95% O2/5% CO2, pH 7.3–7.4) and held at room temperature. Brain slices were then transferred to the recording chamber of a BX-61 microscope (Olympus, PennValley, PA, USA) and superfused with ACSF at room temperature. Medial

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• intermediates, building blocks 4 and 5 (4, R = Me and 5, R = CH2CH2Ph) were synthesized starting with allyldioxazaborolidine 11, an allyl-transfer reagent that was prepared as previously reported (Scheme 3) [27]. Allylation of methyl pyruvate (12) or 13 (synthesized from dimethyl oxalate and phenethylmagnesium

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• (0.5 g/L yeast extract, 0.5 g/L proteose peptone, 0.5 g/L casamino acids, 0.5 g/L glucose, 0.5 g/L soluble starch, 0.3 g/L sodium pyruvate, 0.3 g/L K2HPO4 and 0.05 g/L MgSO4·7H2O, pH 7.2). The cultures were shaken at 160 rpm and 30 °C. After seven days of cultivation the fermentation broth was

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• labeling gave reference compound DMB-Neu5Cyoc(H2) that was analyzed by RP-HPLC-MS (Figure S4, Supporting Information File 1). Additionally, we synthesized the literature known DMB derivatives of the natural sialic acid Neu5Ac [29] and of sodium pyruvate [30] as reference compounds to determine their

• reaction: In a polypropylene vial, the sugar derivatives ManNCp(H2), ManNCyc(H2) and ManNCyoc(H2), respectively, were dissolved in phosphate buffer (100 mM, pH 7.16) to a final concentration of 0.1 M. Sodium pyruvate (15 equiv.) and sialic acid aldolase (a spatula tip) were added. After stirring for 17

• sodium hydroxide (0.5 M, 25 μL). The solutions were analyzed via RP-HPLC-MS. For fluorescence detection (λex = 372 nm, λem = 456 nm), they were diluted with Milli-Q water (1:400). To determine their retention times, the literature known compounds DMB-Neu5Ac and DMB-Sodium pyruvate were synthesized

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• is an unusual cofactor in that, even without the enzyme, it can catalyze many of these reactions [2]. For example, the decarboxylation of pyruvate in water can be accomplished by ThDP, but when it is bound to the enzyme pyruvate decarboxylase (PDC), the decarboxylation rate is increased by 12 orders

• for the APH+ form. However, solid-state NMR using 15N and 13C-labeled ThDP has been used to identify APH+ on pyruvate decarboxylase and the E1 component of the pyruvate dehydrogenase complex [18]. In addition to the plethora of experimental investigations, a number of computational studies have

• , computational studies have been used to investigate full reaction mechanisms of ThDP enzymes, including pyruvate decarboxylase (PDC) [25][26][27][28], benzoylformate decarboxylase (BFDC) [29][30], acetohydroxy acid synthase [24][31][32][33][34][35], pyruvate dehydrogenase (PDH) [36], benzaldehyde lyase [37

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• represent an improvement in the preparation of enantiomerically pure 2 compared with literature data [23]. Höhne et al. obtained only the (R)-enantiomer in 42% yield and 97% ee as a result of kinetic resolution of 1 using ω-transaminase and pyruvate as an amine acceptor. The enantiomeric excess in entries 9

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• Heinrich Warburg in the early 1900s, who was awarded the Nobel Prize in 1931. He proposed that malignant tumor growth relies on aerobic glycolysis, in contrast to normal cells that generate energy by mitochondrial oxidative phosphorylation. The fact that cells converted pyruvate to lactate, even in the

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

• (2 mM, Lonza), non-essential amino acids (NEAA, Sigma-Aldrich Kft), sodium pyruvate (1 mM, Lonza) and penicillin-streptomycine (Lonza). HT-29 human colon adenocarcinoma cells were cultured in RPMI-1640 (Lonza), supplemented with FBS, L-glutamine and penicillin-streptomycine. Cells were maintained in

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• enantioselectivities. The catalytic asymmetric methylation using the simple perfluoroalkylated ketone 3a instead of pyruvate derivatives was further examined (Scheme 3). In contrast to the pyruvate system, the combination of CuTC and BINAP did not facilitate the reaction even at −78 °C, but also afforded the racemic

• fluoroalkylated pyruvate 1 (0.2 mmol) in TBME (0.5 mL) were added over 30 min. The reaction mixture was stirred at the same temperature for 1 h. The reaction mixture was quenched with saturated aq NH4Cl solution. The organic layer was separated and the aqueous layer was extracted twice with Et2O. The combined

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• most used enzymes for the cofactor regeneration are glucose dehydrogenase (glucose to glucuronic acid), lactate dehydrogenase (pyruvate to lactate), glutamate dehydrogenase (α-ketoglutarate to glutamate) and formate dehydrogenase (formate to CO2). In particular, the last enzyme is interesting because

• (88.5 g L−1 d−1) for the epimerization of CDCA to UDCA. However, the employed enzymes have different cofactor specificities, leading to the consumption of stoichiometric amounts of sacrificial substrates (pyruvate and glucose). In addition, substrate loadings in the latter process are still modest (10

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• -(1,2-dihydroquinoline-2-ylidene)pyruvate (91), Yavari and co-workers obtained 4-(2-quinolyl)cyclobutene-1,2,3-tricarboxylic acid triesters 94 and isomeric cyclopentenone derivatives 95 with total yields of 87–94% and a ratio of 1:4 via the intramolecular Wittig reaction. The addition of

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

• ]. VPH catalyzes the addition of water to the C-4 position of 5a to produce (S)-2-keto-4-hydroxypentanoate (6a) [9][10][11]. A retro-aldol cleavage of 6a by pyruvate aldolase yields pyruvate and acetaldehyde (7a). Pyruvate aldolase is tightly coupled with an acetaldehyde dehydrogenase, which uses NAD

• + and coenzyme A to produce acetyl-CoA (8a) [12]. Pyruvate and acetyl-CoA can then be funneled into the Krebs cycle. Over the years, variations of this pathway have been reported that process halogenated catechols. One such pathway is found in Comamonas sp. strain CNB-1, which grows on 4

• the actions of pyruvate aldolase and acetaldehyde dehydrogenase would produce 2-chloroacetaldehyde (7b) and 2-chloroacetyl CoA (8b), which are potential alkylating agents of these enzymes as well as other cellular proteins and DNA. This observation and the potential effects of the halogen on other

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

• isoprenoid precursors are synthesized via the mevalonate pathway (MVA) starting from acetyl-CoA [26]. Alternatively, in the majority of eubacteria, cyanobacteria, green algae and in the plastids of plants isoprenoid biosynthesis originates from glyceraldehyde-3-phosphate (G3P) and pyruvate [26][27

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• enzyme mppR is a pyruvate aldose that catalyses the dehydration/cyclisation of 20 to give cyclic guanidine 21 [52], where transamination by mppQ gives enduracididine (1). Further transformation to L-β-hydroxyenduracididine (5) is then catalysed by mppO [52][53]. Synthetic investigations Synthesis of

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

• dihydrohydroxybenzoates (Scheme 12). The FkbO-subfamily catalyses the formation of 3,4-trans-dihydroxycyclohexa-1,5-dienecarboxylate (69). This reaction is thought to occur via a protonation of the terminal double bond in the enol pyruvate moiety and subsequent attack of water at the cationic position to induce the

• cleavage of pyruvate. To support this mechanism, the enzymatic reaction was performed in 18O-labeled water to yield labeled pyruvate as expected. However, conducting the same experiment for the Hyg5-subfamily of chorismatases, which produce 3-hydroxybenzoate (70), did not yield in any labeled pyruvate

• . This surprising result contradicts an elimination mechanism in the formation of 70 and demands for a new mechanistic proposal. Alternatively, an intramolecular attack at C-3 by the neighbouring hydroxy group at C-4 to cleave the activated pyruvate via an oxirane intermediate can be thought of. To test

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• , and in oxygen-deficiency zones [50]. Reductive tricarboxylic acid cycle The tricarboxylic acid (TCA) cycle is used by all aerobic organisms to generate NADH through the oxidation of small organic metabolites. For pyruvate (11), isocitrate (7) and 2-oxoglutarate (6), oxidation occurs together with a

• through three catalytic steps, and acetyl-CoA (10) which enters central metabolism through a third CO2-fixation step, carried out by ferredoxin-dependent pyruvate synthase to produce pyruvate (11). The carboxylating enzymes are mechanistically complex and highly adapted to the cellular conditions in which

• -hydroxybutyrate cycle [73]. Here acetyl-CoA (10) is initially reductively carboxylated to pyruvate (11), as in the reductive TCA cycle. The pyruvate 11 is phosphorylated with ATP to generate phosphoenolpyruvate (19), followed by a second carboxylation with HCO3− to oxaloacetate by PEPC. Non-autotrophic CO2