The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

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

• concentrations of substrate, the different kinetic preferences of PPK1 and PPK2 can be observed. The implications of these results for the application of PPKs in chemical synthesis and as enzymes for ATP regeneration systems are discussed. Keywords: ATP regeneration; biocatalyst; ePC-SAFT; polyp; PPK

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• -benzo-1,4-thiazines in a yield of 69–85% within 6–11 min [15]. Furthermore, baker’s yeast as whole-cell biocatalyst catalyzed the reaction of 2-aminothiophenols with 1,3-dicarbonyl compounds in methanol and the corresponding 4H-benzo-1,4-thiazines were prepared in 51–82% yield. These reactions were

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• % overall yield starting from compound 11, respectively (Scheme 2). The use of lipase as biocatalyst was employed for the selective acetylation of the primary hydroxy group present in trihydroxy nucleosides 14a,b. This led to the screening of two different lipases, viz Candida antarctica lipase-B (CAL-B

• starting from diacetone ᴅ-glucofuranose were found to be 33.9 and 35.1%, respectively. In our earlier research work, bridged homolyxofuranosylpyrimidines were synthesized following a chemoenzymatic methodology where biocatalyst Novozyme 435 was used for regioselective acetylation of the primary hydroxy

• group present in 3′-O-benzyl-β-ᴅ-glucofuranosylpyrimidines [27]. In this article, regioselective acylation at the primary hydroxy group of 3′-azido-3′-deoxy-β-ᴅ-allofuranosylpyrimidines was carried out with the different biocatalyst Lipozyme TL IM using the same acylating agent, i.e., vinyl acetate but

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• the chemical oxidative cleavage of the 9,11-C–C bond. For the hydroxylation, we used a biocatalyst derived from an Escherichia coli laboratory strain BL21 (DE3) overexpressing the kshA5 and kshB genes from Rhodococcus. rhodochrous. Cortisol (1) was chosen as a model steroidal structure. Results and

• -hydrocortisone, as a substrate [30]. For the construction of the biocatalyst, kshA5 and kshB genes from R. rhodochrous were codon-optimized for enhanced expression in E. coli and cloned into a pET21a protein expression plasmid. To obtain an active biocatalyst, the plasmid was transformed into an E. coli BL21

• have presented the results of the synthesis of the 9,11-secosteroid carbon skeleton by using the designed whole-cell biotransformation of natural steroids with a genetically engineered biocatalyst. The enzymatic oxidation of cortisol derivatives is completely stereo- and regioselective, affording only

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

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

• and in a semi-continuous system. The selected biocatalyst showed good stability under the reaction conditions providing consistent results in terms of conversion and enantiomeric excess after several cycles. The reported results may be of practical interest in view of the development of this

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

• Morten M. C. H. van Schie,
• Tiago Pedroso de Almeida,
• Gabriele Laudadio,
• Florian Tieves,
• Elena Fernández-Fueyo,
• Timothy Noël,
• Isabel W. C. E. Arends and
• Frank Hollmann

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

• areas can be achieved via heterogeneous intake, by bubbling, stirring, etc. Soluble enzymes, however, are often rather unstable under these conditions, possibly owing to the mechanical stress leading to irreversible inactivation of the biocatalyst [7][8]. Methods of bubble-free aeration have been

• high O2-transfer rates thereby enabling efficient and robust oxidase-catalysed oxidation reactions. Results and Discussion Selection and characterisation of the biocatalyst As biocatalyst for this study we focussed on the recombinant aryl alcohol oxidase from Pleurotus eryngii (PeAAOx) [28][29][30][31

• ), [trans-hex-2-enol]0 = 40 mM, [PeAAOx] = 0.02 µM, [catalase] = 600 U mL−1. The TN value was calculated based on the GC yield of every run. The TN was obtained by dividing the product concentration (as determined chromatographically) by the biocatalyst concentration. Enzymatic reaction schemes for the

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

• the half-life (23 h) is lower and the biocatalyst can be reused for only five cycles of conversions. In order to reduce the mechanical stress that might inactivate the immobilized enzymes, the flow-system represents a valid technology. The packed-bed reactor set up by Zheng et al. partially solved

• process. Several examples are reported in literature about substrate or product inhibition of HSDHs. Protein engineering could help to solve or lowering the effect of these issues, leading to the optimization of the biocatalyst for industrial applications. In addition, the use of flow-reactors can be

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

• Neha Rana,
• Manish Kumar,
• Vinod Khatri,
• Jyotirmoy Maity and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2017, 13, 2078–2086, doi:10.3762/bjoc.13.205

• lipase as biocatalyst. Similar applications of lipases have been reported for the separation of mixtures of arabinofuranosyl and -pyranosyl nucleosides [12], O-aryl α,β-D-ribofuranosides, etc. [13][14][15]. We herein report for the first time the use of Novozyme®-435 for the separation of an epimeric

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

• sugar donor scope, and our group has shown the potency of this enzyme as a biocatalyst for the chemoenzymatic synthesis of non-natural desulfoglycosinolates [22]. More recently, S-glycosylated peptides have been identified, and characterized. In bacteria the structures of sublancin [23], glycocin F [24

• , the inactivation of the acid/base catalytic residue is of particular interest, and can lead to an original biocatalyst with poor hydrolytic activities but the ability to promote the formation of thioglycosidic linkages (Figure 7). Such mutated enzymes were firstly described by the team of Withers and

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• the advantages of enzyme catalysis and mechanochemistry. Under the described conditions, the primary aliphatic hydroxy groups present in the substrates were selectively modified by the biocatalyst to afford monoesterified products. Amongst the tested lipases, CALB proved to be the most effective

• biocatalyst for these transformations. Noteworthy, various acyl donors of different chain lengths were tolerated under the mechanochemical conditions. Keywords: ball milling; enzymes; esterification; lignin derivatization; mechanochemistry; Introduction Mechanochemical reactions, particularly those carried

• ; right). To corroborate the role of the biocatalyst in the esterification, the experiment was repeated with sodium hydroxide in place of CALB. Consequently, after 2 h of milling the reaction only generated the diacetylated product erythro-4a (Scheme 2; left). These results reflect the high selectivity of

Characterization of non-heme iron aliphatic halogenase WelO5* from Hapalosiphon welwitschii IC-52-3: Identification of a minimal protein sequence motif that confers enzymatic chlorination specificity in the biosynthesis of welwitindolelinones

• Qin Zhu and
• Xinyu Liu

Beilstein J. Org. Chem. 2017, 13, 1168–1173, doi:10.3762/bjoc.13.115

• engineering and evolution of these proteins for biocatalyst application. Keywords: alkaloid biogenesis; biosynthetic divergency; C–H activation; halogenase; non-heme iron enzyme; Introduction Carbon–halogen (C–X) bonds are prevalent structural motifs in modern agrochemicals, pharmaceuticals and bioactive

• sequence motif, initially discovered in the comparative characterization of WelO5 and AmbO5 [18]. This further confirms the functional significance of this conserved sequence motif in this new halogenase family that may guide the rational engineering and evolution of these proteins for biocatalyst

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

• synthases do not comprise combinations of Class I/Class II domains but contain both a prenyltransferase domain and a terpene synthase moiety. This combination of catalytic modules allows the direct formation of the isoprenyl diphosphate substrate for the terpene synthase in a single biocatalyst. An unusual

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• transglycosylation reaction of the corresponding thioxopyrimidines employing thymidine as a donor of the carbohydrate residue and E. coli TP as a biocatalyst [35]; 6-azauracil (3a) and 6-azathymine (4a) displayed no substrate activity in analogous reactions (cf. [26][27][28][29]). These studies prompted us to

• and 2-thiothymine into the corresponding 2'-deoxyribosides in 54 and 61% yields, respectively, employing thymidine as a donor of the pentofuranose moiety and TP (Sigma) as a biocatalyst; the TP quantity and the reaction conditions are not indicated. The discrepancy between our results and those by

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• -value chemicals. This holds true also for enzyme-catalyzed transesterification reactions. To cite a few examples, the literature claims the use of lipase as a biocatalyst for i) the reaction of glycerol with DMC for the synthesis of glycerol carbonate (GlyC) under solvent-free conditions. A 60% yield

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• organic media or ionic liquids as co-solvents [24][25][26][27]. The enzymatic transglucosylation using 4-nitrophenyl β-D-glucopyranoside as the donor and almond β-glucosidase as biocatalyst gave salidroside (2) in moderate yield [28]. Recently, we have published the enzymatic glycosylation of tyrosol (2

Highly stable and reusable immobilized formate dehydrogenases: Promising biocatalysts for in situ regeneration of NADH

• Barış Binay,
• Dilek Alagöz,
• Deniz Yildirim,
• Ayhan Çelik and
• S. Seyhan Tükel

Beilstein J. Org. Chem. 2016, 12, 271–277, doi:10.3762/bjoc.12.29

• C. boidinii FDH prepared with dextrane polyaldehyde and glutaraldehyde showed 3.6 and 4.0 folds higher stability than the free FDH at 50 °C. It is an important feature to reuse a biocatalyst for many cycles without loss of initial activity. In this study, the operational stability of immobilized

• potential candidate for the immobilization of enzymes and the immobilized FDHs, especially FDHIALD, is a robust biocatalyst and it may be used in the combination with other dehydrogenases to regenerate NADH. Experimental Nicotinamide adenine dinucleotide hydrate (NAD+) was purchased from Acros Organics (New

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

• ]. In the O2-rich environments in which it operates, this property makes RuBisCO a particularly inefficient biocatalyst and a major bottleneck to C3 carbon fixation. Through evolution, RuBisCO has adapted to rising oxygen concentrations by developing higher specifities for CO2 at the expense of

• catalysts were able to catalyse hydrogenation of CO2 to similar levels as Pd adsorbed on activated carbon [127]. In the previously mentioned work [118] on the purified acetogenic FDH-hydrogenase complex from Acetobacterium woodii, a whole-cell biocatalyst was also reported, generating high yields of formate

• ]. Such reactions may be performed in vitro, where the relative amounts of each biocatalyst and the intermediate concentrations during the reaction can be closely monitored and controlled. However, this is accompanied by a requirement in cost related to enzyme purification, proportional to the number of

Engineering Pichia pastoris for improved NADH regeneration: A novel chassis strain for whole-cell catalysis

• Martina Geier,
• Christoph Brandner,
• Gernot A. Strohmeier,
• Mélanie Hall,
• Franz S. Hartner and
• Anton Glieder

Beilstein J. Org. Chem. 2015, 11, 1741–1748, doi:10.3762/bjoc.11.190

• . pastoris Δdas1 Δdas2 strain is capable of supplying the actual biocatalyst with the cofactor over a longer reaction period without the over-expression of an additional cofactor regeneration system. Thus, focusing the intrinsic carbon flux of this methylotrophic yeast on methanol oxidation to CO2 represents

• linking methanol to biomass production, were deleted. In the course of 38 h, the optical density of the P. pastoris Δdas1 Δdas2 cultures on methanol doubled. This remaining carbon flux into cellular metabolism might also enable the continuation of protein expression and thus biocatalyst production, while

• P. pastoris strain. These findings are of importance for the use of the knock-out strains in whole-cell processes, as impairments in recombinant protein production, i.e., the production of the actual biocatalyst, would reduce its applicability. NADH-dependent biotransformations performed in knock

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• manner. Given that P450cam is a robust biocatalyst with good activity for this class of enzymes, a library of active site mutants with diversity in amino acid side chains lining up the substrate pocket would demonstrate a valuable resource for the development of useful P450cam based biocatalysts. The

• domain of P450-RhF (RhFRed) [17][18][19]. This chimera, named P450cam-RhFRed, operates without the need for additional reductase partners and retains the native activity of non-fused P450cam in the selective oxidation of camphor to 5-exo-hydroxycamphor. When generated as a whole-cell biocatalyst in

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• design of mixed biocatalyst pathways for the comprehensive oxidation of cholesterol, and, at the same time, the acquisition of frequent answers with an individual application for biosensorics is of major interest. Sophisticated sensing arrangements including single and complex selective agents may be

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• and (R)-(−)-7 enabling to continue the planned synthesis. Each of the reaction parameters and up-scaling approaches are discussed in detail in the following paragraphs. Biocatalyst effect on the kinetic resolution of (±)-3 The enzymatic kinetic resolution of (±)-3 was initially attempted using a

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• ]. AMPDA is commercially available as a practical lyophilate powder and was widely used in the food industry for the production of inosine 5′-phosphate. AMPDA is a more versatile biocatalyst compared to ADA, since it can convert a larger number of adenosine derivatives into the corresponding inosine

• derivatives. AMPDA was used as a biocatalyst in the enzymatic hydrolysis of adenosine 15. The reaction proceeded smoothly in the presence of AMPDA in phosphate buffer at pH 5.6 and 40 °C with 3% DMSO as a co-solvent. Adenosine 15 was enzymatically deaminated to give trachycladine B in almost quantitative