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

• reasons, the synthesis of N-acetylneuraminic acid (Neu5Ac) in a continuous fixed-bed reactor by an immobilized epimerase and aldolase was investigated in detail. The immobilized enzymes showed high stability, with half-life times > 173 days under storage conditions (6 °C in buffer) and reusability over 50

• 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

• under investigation [9][10][11]. For this study, the enzymatic synthesis was chosen for its simple reaction sequence (Figure 1) and high selectivity. Different research groups already described the reaction kinetics of the epimerase and aldolase at ambient pressure [5][8]. In this study, the rate

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• . Other examples of the use of column reactors for the catalysis of aldol reactions include: The use of immobilised aldolase enzymes for the synthesis of carbohydrates [114] and the use of a calcinated hydrolactite-packed column for the condensation of furfural with acetone [115], however, this still

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

• generate new pterin amides (Figure 1) [14][17]. The same process used in generating RTA inhibitors was later used as a key step in the development of new aldolase reductase inhibitors [8]. The benefit of DBU as an additive in these previous reports was largely empirical, and reaction times were still in

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

• acid aldolase reaction delivered the corresponding sialic acids. After RP-HPLC purification, they were labeled with DMB and the final reference compounds were analyzed by RP-HPLC-MS (Figures S2 and S3, Supporting Information File 1). The synthesis of cyclopropane derivative Ac4ManNCyoc(H2) is shown in

• Scheme 3. Alcohol 4 was activated with 4-nitrophenyl chloroformate, and the obtained carbonate 5 reacted with neutralized mannosamine and peracetylated as described above to give Ac4ManNCyoc(H2) in a yield of 57%. Deacetylation with N,N-ethyldimethylamine in methanol and further aldolase reaction and DMB

• mg, 84%) which was used without further purification for the aldolase reaction. ManNCyc(H2): Ac4ManNCyc(H2) (67 mg, 0.16 mmol) was dissolved under nitrogen atmosphere in dry methanol (4.5 mL) and sodium methoxide (0.5 M, 0.05 mL) was added. After stirring overnight, Amberlite IR 120 was added for

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

• ]). The ability of peptide dendrimers to perform catalysis in an aqueous environment has also been investigated [105]. Many different libraries of peptide dendrimers have been used for biocatalytic applications, such as hydrolysis and aldolase reactions [105][106][107][108], showing their potential in

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

• 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

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• transferred to a glycan acceptor in a glycoprotein by a sialyltransferase [32][33]. A chemoenzymatic method for its preparation is shown in Scheme 1. It is based on the coupling of Fmoc-glycyl-mannosamine with pyruvate catalized by SA-aldolase to afford the N-protected sialic acid. After reaction with CTP

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• well as product purification remain problematic. Our lab mainly focuses on the in vitro production of rare sugars using dihydroxyacetone phosphate (DHAP)-dependent aldolases. In our previous work, we utilized L-fuculose-1-phosphate aldolase (EC 4.1.2.17) from Thermus thermophilus HB8 (FucAT.HB8) to

• significantly cheaper starting material D-gulono-1,4-lactone instead of expensive L-glucose. In our previous work, we discovered that two rare sugars, D-sorbose and D-psicose, were simultaneously generated when L-rhamnulose-1-phosphate aldolase (RhaD, EC 4.1.2.19) [47] catalyzed the aldol addition between DHAP

• synthesis of L-tagatose was easily achieved by employing the previous discussed cost-effective one-pot four-enzyme system containing L-fuculose-1-phosphate aldolase (FucA, EC 4.1.2.17) (Scheme 7). In this case, L-glyceraldehyde was used as the aldol acceptor and L-tagatose and L-fructose were obtained

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• aldolase (TA) from Thermotoga maritima was immobilized on an Eupergit support by both a direct and an indirect method. The incubation time for the direct immobilization method was optimized for the highest amount of enzyme on the support. By introducing the immobilized TA in a packed-bed microreactor, a

• was achieved at 20 minute residence time. Finally, the productivity of the reactor was calculated, extrapolated to parallel run units, and compared with data collected previously. Keywords: Eupergit; flow chemistry; immobilized enzyme; threonine aldolase; Introduction Enzymes are bio-based catalysts

• which is useful to reduce the cost of the process by reusing the catalyst. Conclusion To the best of our knowledge, we report the first use of immobilized threonine aldolase in a microreactor for the flow synthesis of phenylserine. So far, we achieved a maximum of about 30% yield under the typical flow

Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

• Dinesh Simkhada,
• Huitu Zhang,
• Shogo Mori,
• Howard Williams and
• Coran M. H. Watanabe

Beilstein J. Org. Chem. 2013, 9, 1768–1773, doi:10.3762/bjoc.9.205

• implicated a pyruvate aldolase and methyltransferase containing gene cluster as well as potential polyketide gene clusters containing methyltransferase genes, which will be evaluated in due course through genetic knockout experiments of the ΔaziA2 mutant strain. Disruption of the aziA2 gene gave

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• catalyzed the epimerization of 14 yielding the epimer N-acetylmannosamine (15), which consequently was condensed by the second enzyme aldolase with pyruvic acid (16) to form the product 17 (Scheme 6). By appropriately adjusting the reaction parameters, such as pH, temperature and substrate concentrations

• -acetylneuraminic acid (17) in a continuously operated enzyme membrane reactor. E1: Epimerase; E2: Aldolase [27]. Chemo-enzymatic epoxidation of 1-methylcyclohexene (18) in a packed-bed reactor (PBR) containing Novozym 435 (E) [28]. Continuous production of (R)-1-phenylethyl propionate (24) by dynamic kinetic

• -phospho-D-glycerate (57) into D-ribulose 1,5-bisphosphate (58) in a cascade of packed-bed reactors. E1: Phosphoglycerate kinase; E2: Glycerate phosphate dehydrogenase; E3: Triose phosphate isomerase; E4: Aldolase/FBP; E5: Phosphatase/FBPase; E6: Transketolase; E7: Aldolase/SuBP; E8: Phosphatase/SBPase; E9