Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• , respectively (Figure 3). Biochemical studies show that histamine and phenethylamine moieties were produced from histidine and phenylalanine substrates by a decarboxylase enzyme [41][42][43]. Pseudomobactin A (4) was proposed logically to have formed through direct amination of the unstable salimethyloxazolinyl

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• examples, and the advance of anion-binding-catalyzed strategies involving more complex H-bonding networks clearly highlight that it is indeed possible to mimic enzyme-like structures with small-molecule catalysts for asymmetric synthesis. Conclusion In the past two decades, tremendous advances in the field

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• 10.3762/bjoc.17.144 Abstract The enzyme tyrosine kinase BCR-Abl-1 is the main molecular target in the treatment of chronic myeloid leukemia and can be competitively inhibited by tyrosine kinase inhibitors such as imatinib. New potential competitive inhibitors were synthesized using the (phenylamino

• -4 of the triazole nucleus. All compounds were evaluated for their inhibitory activities against a chronic myeloid leukemia cell line (K562) that expresses the enzyme tyrosine kinase BCR-Abl-1 and against healthy cells (WSS-1) to observe their selectivity. Three compounds showed promising results

• the transduction of signals; these processes induce cell apoptosis [8][9]. As mutations in the BCR-Abl-1 enzyme domain can occur, cases of resistance have emerged in the treatment with TKIs, compromising its effectiveness [10][11]. In continuation of the work by our group to develop new imatinib

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• (LG, e.g., phosphate, fluoride, nucleotide) are polymerized by the enzyme to form the desired polysaccharide (Figure 1A). Several classes of enzymes are available, including hydrolases, phosphorylases, sucrases, glycosyltransferases, and glycosynthases [19][20][21][22]. An excellent overview of the

• enzymes available for polysaccharide synthesis and their mode of action was recently published [11]. Despite the numerous advantages of this approach, limited enzyme availability as well as their high specificity narrowed the substrate scope. Generally, the highly specific enzyme reactive site tolerates

• polymerization of cellobiose fluoride 1 was achieved using a cellulase produced from Trichoderma viride (Scheme 1A). The DP of the acetylated product was shown to be at least 22. Using a purified version of this enzyme, it was possible to obtain a synthetic analogue of Cellulose I [64]. A rough control of DPs

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• in good yields (Scheme 39C). The authors used the same methodology to synthesize two 4H-benzo[d][1,3]oxazin-4-one derivatives that act as inhibitors of two enzymes (compounds 130 and 131 in Scheme 39D). The first one is the enzyme C1r serine protease, involved in both inflammation and renal scarring

• [199], and the second one is the enzyme elastase, responsible for consuming elastine, leading to aging processes [200]. Beyond that, 4H-benzo[d][1,3]oxazin-4-one derivatives 126–129 have been studied as potential hypolipidemic drugs (Scheme 39A) [201]. Beyond the above-cited

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• methionine aminopeptidase type-2 (MetAP-2) enzyme [129]. MetAP-2 is involved in cell proliferation, translation and post-translational modifications of nascent polypeptides and is therefore essential for cell viability [130][131]. Additionally, fumagillin is also known to be overproduced upon caspofungin

• with the prenylation of ʟ-tryptophan to dimethylallyltryptophan (DMAT). During several steps DMAT is converted to chanoclavine-I aldehyde, the last mutual intermediate. Branching into different pathways after this intermediate is mainly due to differences in the function of EasA, the enzyme catalysing

• hydroxylated and methylated to tryprostatin A. Oxidative closure of the ringstructure then results in fumitremorgin C. Further modification of the structure leads to fumitremorgin B and verruculogen, which shares the same pathway [97][160][161][162]. Which enzyme is responsible for the conversion of

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• attached. In particular, such extensions may be initiated by members of the B4GALT family or B3GALNT2. Specific variants are noted on α-dystroglycans. 14) O-linked fucose: This pathway includes POFUT1, the enzyme responsible for the addition of fucose to Ser/Thr residues. MFNG, LFNG, and RFNG can attach

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• Cladosporium sp. emitted (E)-β-caryophyllene (1) in culture (Table 2, Figure 1). As this sesquiterpene is also a characteristic VOC in the constitutive and herbivore-induced blends of black poplar [57][58][59], we wanted to identify and characterize the responsible fungal terpene synthase, as this enzyme could

• sesquiterpene product was formed by each TPS: CxTPS1 produced (E,E)-α-farnesene (12) and CxTPS2 produced (E)-β-caryophyllene (1). With GGPP, no enzyme activity was recorded for CxTPS2, while CxTPS1 converted this substrate to (E,E)-β-springene (13) as the minor compound and major amounts of (E,E,E)-α-springene

• ). CxTPS1 was a multifunctional enzyme in vitro and produced the monoterpenes myrcene (9) and (E)-β-ocimene (10) from GPP, the sesquiterpene (E,E)-α-farnesene (12) from FPP, and the diterpenes (E,E)-β-springene (13) and (E,E,E)-α-springene (14) from GGPP. CxTPS2, in contrast, showed a narrower substrate

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• medicinally active as well as smart functional materials possessing the pyrrole as a fundamental subunit [28][29][30]. Additionally, 3,4-disubstituted pyrrole derivatives are versatile building blocks for the production of diverse bioactive molecules like co-enzyme, alkaloids, porphyrins and other related

Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV

• Santiago Ramos-Carreño,
• Ivone Giffard-Mena,
• Jose N. Zamudio-Ocadiz,
• Alfredo Nuñez-Rivera,
• Ricardo Valencia-Yañez,
• Jaime Ruiz-Garcia,
• Maria Teresa Viana and
• Ruben D. Cadena-Nava

Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95

• ]. Also, the CCMV VLPs are resistant to enzyme degradation through the digestive tract [32][33][34]. It is to be kept in mind that possibly the shrimp’s virus, in contrast to CCMV VLP’s, needs specific receptors to be internalized in the shrimp cells. For these reasons, CCMV VLPs show quite an advantage

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

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• -pong second (ketone amination, diol esterification, desymmetrisation in the second half reaction); ping-pong first (diol ester hydrolysis) and ping-pong both (prochiral diacids). For plausible values of enzyme kinetic parameters, the product enantiomeric excess (ee) can decline substantially as the

• reaction proceeds to high conversion. For example, an ee of 0.95 at the start of the reaction can decline to less than 0.5 at 95% of equilibrium conversion, but for different enzyme properties it will remain almost unchanged. For most mechanisms a single function of multiple enzyme rate constants (which

• study if and how the product ee declines at high conversion. Keywords: enantiomeric excess; enzyme; kinetic mechanisms; kinetic parameters; prochiral; Introduction There is great interest in using enzymatic catalysis in the synthesis of homochiral molecules. An early approach was to use

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• produced by the actions of the 10 enzymes included in the model. The different ganglioside nomenclature systems in common use are compared and a systematic variant of the widely used Svennerholm nomenclature is described. Knockouts of specific enzyme activities are used to simulate congenital defects in

• O-linked glycosylation, with a web-based application, O-Glycologue, that allows knockouts of enzymes of O-linked glycosylation and the assignment of custom “wild type” sets of enzyme activities to study the effects of differential knockouts on the resultant networks [15]. In this article, we

• describe an extension of this method to gangliosides, and to the enzyme reactions associated with their biosynthesis. The formalism and the associated web application, now renamed Glycologue, provide a way to explore the effects of mutations that result in a loss of functionality, or promotion of disease

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• commonly used for the synthesis of biologically active compounds having enzyme inhibition and antiviral activity [1][2], and are found in the structures of many commercially available antidepressant drugs [3][4][5][6][7][8][9][10][11][12]. In addition, dibenzosuberenone (1) and polyconjugated derivatives

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• increased in the presence of avibactam (4 mg/L) in all bacterial strains under observation. The MIC values of MER without avibactam were observed to be in the range of 2 mg/L to 4 mg/L, whereas after the addition of avibactam the antibacterial activity changed to <0.125 mg/L–1 mg/L, indicating the enzyme

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• diphenyldiazomethanes, available reagents carrying substituents on the phenyl rings. For example, covalent attachment of C60 to peptides is performed through a phenyl spacer, as it was demonstrated in a synthesis of fulleride 27 [89]. The latter compound was designed specifically for suppressing a HIV enzyme. The

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

• microwave irradiation, a mixture of monoacylated and diacylated products 3 and 4 in 52% and 33% yield, respectively, was isolated [28]. Enzymatic hydroxylation 3-Ketosteroid 9α-hydroxylase (KSH) from R. rhodochrous has been shown to oxidize C9 in several steroids [29]. This enzyme consists of two

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• -volatile precursor that is stored in garlic and related plants and only degraded into sulfur volatiles upon wounding by the pyridoxal phosphate (PLP) dependent alliinase (Scheme 1B) [7]. This initial enzyme-catalyzed reaction yields one equivalent of allylsulfenic acid (10), pyruvic acid (11), and ammonia

• giving another example for the complex interactions between marine bacteria and algae. Known DMSP degradation pathways include its hydrolysis to dimethyl sulfide (DMS) and 3-hydroxypropanoic acid (15) by the enzyme DddD [19], or the lysis to DMS and acrylic acid (16) for which various enzymes including

• DmdABCD is fully established in P. inhibens, while genes for DmdD are missing in D. shibae and O. indolifex, suggesting that another enzyme with a low sequence homology may substitute for DmdD, leading to allylthiol and several sulfur volatiles derived from it in all three strains. The DMSP hydrolase DddD

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• and phosphonate-linked analogues of naturally occurring peptides. They are more stable than phosphonopeptides and have been widely applied as enzyme inhibitors, haptens for the production of antibodies, biological agents, and prodrugs. The synthetic strategies towards phosphonodepsipeptides are

• than the corresponding phosphonopeptides because the phosphonate bond is more inert than a phopshonamidate bond. Phosphonodepsipeptides are widely used as enzyme inhibitors [6][7][8][9][10], haptens for inducing catalytic antibodies [11][12], and produgs [8][9][13]. They have potential applications as

• -diazoalkylphononates can be readily prepared from the corresponding 1-aminoalkylphosphonates via nitrosation with amyl nitrite. Conclusion Phosphonodepsipeptides are phosphorus analogues of depsipeptides. They are more stable than the corresponding phosphonopeptides and have been widely used as enzyme inhibitors

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• hydroxylating enzyme in E. coli has been previously achieved [36][37]. Bacterial prolyl hydroxylases have been characterized, and they are able to oxidize proline and analogous structures in recombinantly expressed proteins [38]. Nonetheless, we are still missing evidences of natural posttranslational

• example, the volume difference between Pro and Dfp is smaller than the difference between Val and Ile. It is therefore not surprising that Flp and Dfp can in principle be recognized as proline by natural enzyme binding pockets. The successful experimental incorporation of fluoroprolines into proteins

• based on the recognition of fluoroprolines by the native enzyme aminoacyl-tRNA synthetase (vide infra) proves this assumption. 2.2 Local polarity Another important feature of fluoroprolines is their local electrostatic potential (local polarity). In proline, position 4 contains a positive surface

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• TFMK moiety is a proven effective metal chelator in various enzyme inhibitors (Figure 1b) [58][59][60][61][62][63][64][65]. Several useful methods exist for preparing trifluoromethyl ketones [66][67], such as the direct trifluoromethylation of esters by the Ruppert–Prakash reagent (Me3SiCF3) [68][69

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• was sought. The possibility to exploit the use of an enzyme to derivatize benzyl alcohol into an easily separable species was an intriguing opportunity. To integrate such a biocatalyzed transformation into the continuous Curtius rearrangement process, immobilized CALB, a robust hydrolase enzyme was

• immobilized CALB enzyme is reported. This approach enabled the chemoselective derivatization of benzyl alcohol into the readily removable benzyl butyrate thus simplifying the final purification stages. The resulting Cbz-carbamates were furthermore elaborated into derivatives of β-amino acids via biphasic flow

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• 78 was incubated in the presence of IPP and the enzyme prenyltransferase, a rate of 5.1 × 10−4 nmol⋅min−1⋅mg−1 was measured for the condensation reaction (Scheme 24), which is to be compared to a value of 7.4 × 102 nmol⋅min−1⋅mg−1 observed for the condensation involving IPP and geranyl pyrophosphate