Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• intermediate in flavonoid biosynthesis and is much more ubiquitous than avenalumic acid. In general, p-coumaric acid is synthesized by phenylalanine ammonia-lyase and cinnamate 4-hydroxylase from phenylalanine or by a tyrosine ammonia-lyase from tyrosine [26]. However, the Cma system synthesizes p-coumaric

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• carboxylate anion and/or reduction of the corresponding N-hydroxyphthalimide- (NHPI)-derived redox-active ester, although it destroys their stereochemical information [46][47][48][49][50][51]. In addition, the side-chains of aromatic amino acids (mainly electron-rich tryptophan and tyrosine) can be

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• potential in the synthesis of various tyrosine kinase inhibitors, including hesperadin and the approved drug nintedanib. The key step of the synthesis involves the Eschenmoser coupling reaction (ECR) between a substituted 3-bromooxindole 1 and appropriate primary, secondary or tertiary thioamides which

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• elucidate the chemical structures of the isolated compounds [19]. 2 Synthesis 2.1 Biosynthetic pathway In the literature, there are two possible biosynthetic pathways for the formation of these compounds. The first one was proposed by Pettit and co-workers [16][17] based on tyrosine as the starting material

• . An o-phenolic coupling between two units of tyrosine furnishes the intermediate Int-1, which by deamination, selective reduction of one of the carboxylate groups, macrolactonization, and subsequent structural modifications would lead to the aforementioned combretastatins D (Scheme 1). The second

• pathway was proposed by Ponnapalli and co-workers [14] and was initially based on the conversion of phenylalanine into tyrosine by phenylalanine hydroxylase and m-tyrosine via radical hydroxylation (Scheme 2). Subsequent deamination of tyrosine, with concomitant hydroxylation/deamination of m-tyrosine

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• structure of spirolactam 157 to access the family (Scheme 13). To synthesize it, they conjectured that a tyrosine amino acid, a cyclohexadione derivative, and a nonracemic dehydroalanine derivative could be effectively combined to build the core structure, using an already known iridium-photocatalyzed

• radical reaction [87]. Indeed, when ʟ-tyrosine methyl ester (154), 1,4-cyclohexanedione monoethylene acetal (155), and dehydroalanine derivative 156 were allowed to react in the presence of TFA, molecular sieves, 1 mol % of fac-Ir(ppy)3, and Hantzsch ester under blue LED irradiation at 40 W, this resulted

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• , glycogen synthase kinase 3 (GSK-3), leucine-rich repeat kinase 2 (LRRK2), tyrosine phosphorylation-regulated kinase-1A (DYRK1A) and CDC2-like kinase 1 (CLK1), and fatty acid amide hydrolase (FAAH) [4]). Similar properties were ascertained for 1-deazapurine derivatives (imidazo[4,5-b]pyridines) and

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• since the 1960s [15][16]. Stable-isotope labeling experiments confirmed that ʟ-tyrosine or ʟ-phenylalanine are involved in the biosynthesis of p-terphenyl as metabolic origin. The precursors undergoing deamination are converted to the corresponding α-keto acid, then a quinone intermediate arises by

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• tyrosine (Tyr-56) residue, which likely fulfills a similar coordinative function. Furthermore, a conserved arginine residue (UbiA-297 R145) was detectable, which was located in the neighboring α-helix (R145) and in proximity to the binding motif, and was hypothesized to be involved in the coordination

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• activates the catalytic tyrosine residue, while the cyclooxygenase-site catalyzes the formation of di-peroxides. The active site of the peroxidase-site contains a heme cofactor in the solvent-exposed cleft on the opposite side of the membrane binding domain. Although the heme cofactor is located in the

• enzymes with tetranitromethane, a reagent for tyrosyl residue nitration, eliminated the cyclooxygenase activity, while the activity was not abolished in the presence of the cyclooxygenase inhibitor indomethacin, indicating that the tyrosine residue(s) is the catalytic center for endoperoxide formation

• . The sequence analysis of the tetranitromethane-treated enzyme indicated that three tyrosine residues, Tyr355, Tyr385, and Tyr417, were only nitrated in the absence of indomethacin (Figure 2A) [62]. A subsequent mutagenesis study of these residues indicated that the Tyr385 residue plays the catalytic

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• , entry 1). Since the reaction seemed to stop after 30–40% conversion, it was speculated that the ester enolate chelate complex formation was incomplete due to consumption of the base. For instance, deprotonation of tyrosine residues in benzyl position has been observed previously in the derivatization of

Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

• Qiuxin Zhang,
• Weiyi Tan and
• Bing Xu

Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17

• 2f and 2g results in 10a and 10b. 9 and 10 would help test the effects of additional N-terminal modifications. To examine the necessity of enzymatic dephosphorylation, we replaced ᴅ-phosphotyrosine (py) in 2g, 2h, 6a–c by ᴅ-tyrosine to yield 11a, 11b, 12a–c, respectively. Attaching N-methylpyrrole on

• the designed peptides combines solution synthesis of the enzyme trigger or the fluorophore with the solid-phase synthesis of the pyrrole-peptide conjugates. We used phosphorus pentoxide and phosphoric acid to react with ᴅ-tyrosine, ʟ-tyrosine, ʟ-serine, or ᴅ-serine to produce ᴅ-phosphotyrosine, ʟ

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• particular enzymes. Preliminary results indicate that scaffold C shows good affinity to proto-oncogene tyrosine-protein kinase Src, a well-known anticancer target [47], with IC50 = 0.26 µM and is a suitable candidate for further structural optimization. Paullone related indolobenzazepinone isomers. 7,12

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• evaluated against their antioxidant activity and exhibited promising activity. Protein tyrosine phosphatase 1B (PTP1B) is essential in the dephosphorylation of the activated insulin receptor, and inhibition of this enzyme would be an excellent strategy for the treatment of type 2 diabetes. Ahn and co

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• of macrocycles [49]. The macrocyclisation technique by tryptophan C2–H activation has been further improved showing structurally constrained peptides bearing a side chain connection of tryptophan and phenylalanine or tyrosine [50]. Moreover, a similar Pd-mediated approach for C(sp3)–H activation of

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• ) with relevant biological activities, is recognized as a privileged scaffold in medicinal chemistry [3][4]. Among important quinazoline derivatives, 4-anilinoquinazolines have been widely investigated as antitumor agents because they can inhibit some receptor tyrosine kinases (RTKs) expressed by

(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

• in the docking studies. Keywords: chronic myeloid leukemia; 1,3-dipolar cycloaddition; imatinib; (phenylamino)pyrimidine-pyridine; 1,2,3-triazole; Introduction Changes in tyrosine kinase proteins (TKPs), either by mutation or chromosomal translocation, can turn them into potent oncogenes

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• -hydrogen in the diallylsulfoxide (123) did not allow any Pummerer rearrangement [88][89]. Selenides In 1997, Showalter synthesized bis(indol-2-yl)selanes (or selenides) 130 having potential tyrosine kinase inhibitor activities [90][91]. The synthesis was achieved by reacting diselenium dichloride with (R

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

• [143][144][145]. Three types of melanins are known to be produced by fungi of which A. fumigatus is able to produce two – pyomelanin and dihydroxynaphthalene melanin (DHN-melanin). While the water-soluble pyomelanin is synthesized via the tyrosine degradation pathway, the DHN-melanin synthesis relies

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• employing a variety of amino esters and a wide range of (hetero)aromatic and alkyl ketones. Natural products, such as 5α-cholestan-3-one and dihydrotestosterone, were also tolerated, affording a new strategy to modify biologically active compounds. Amino acids, such as tyrosine, ʟ-Phe-ʟ-Phe, glutamic acid

• (n = 1–3). For azides with n = 3, the reaction was performed using alkynes bearing rather complex R2 substituents, such as tyrosine, glucose, clofibrate, vitamin E, estrone, and oleanane triterpenes, which tolerated the reaction conditions and afforded the corresponding triazoles 77 fused with a six

• were screened, producing a moderate to high yield of the desired products. Moreover, alkynes based on complex molecules, such as glucose, tyrosine, clofibrate, estrone, oleanane triterpenes, and vitamin E tolerated the reaction conditions and afforded the corresponding triazolo disulfides (Scheme 28

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• therapeutic potential. In addition, trans-4-phenyl-N,N-dimethyl-2-aminotetralin (trans-H2-PAT, 4, Figure 1) [6] has been determined to modulate tyrosine hydroxylase activity and dopamine synthesis in rodent forebrain and is also a ligand binding to histamine H1 receptors, and thus is a potentially useful

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• tyrosine [16] (pFtBTyr, 9) and proline [17] (4R and 4S-pFtBHyp, 10 and 11, Figure 1) have also been utilised as 19F NMR probes, both showing promise as valuable tools for biomolecular studies. Particularly impressive is that by incorporating pFtBTyr (9) into a model peptide, Tressler and Zondlo were able

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• inhibitory activity against three tyrosine kinases (EGFR, VEGFR-1, and c-Met) [5]. As mentioned, it is accessible through the reduction of dehydroaltenusin with zinc powder in acetic acid with intermediate formation of altenusin [1]. Nevertheless, this route cannot be considered as a viable approach to this

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• sulfated tyrosine and sialyl-LewisX as model ligands. The resulting signal is referenced to a control experiment lacking the preincubation of L-selectin particles. Figure 3 summarizes the resulting dose–response curves. The sulfated supramolecular assemblies resulting from II bound with an IC50 value of

• ) measured by SPR. L-Selectin-coated nanoparticles were preincubated with solutions of the supramolecular polymers. Their affinity towards multimerized artificial ligands composed of sulfated tyrosine and sialyl-LewisX, immobilized on an SPR-chip was probed. The binding signal is plotted relative to a sample

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• allows the conjugation of the cleavable side chain, and tyrosine provides additional aromatic–aromatic interactions, as shown in a recent cryo-EM structure (PDB: 6X5I) [41]. Based on the above rationale, the DEDDDLLIG sequences attach to the ε-amine of the lysine residue of the tetrapeptide Nap-ffky to