Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• complexity of chemical synthesis towards novel drugs has almost doubled from eight chemical steps to an average of 14 in 2021 [1]. Therefore, the need for robust reactions compatible with many functional groups in complex molecules is an integral part in contemporary medicinal chemistry and drug development

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• -inflammatory properties, hepatorenal protection, and anticancer activity. They are often used as coloring and seasoning agents. Due to the limited content of crocins in plants and the high cost of chemical synthesis, the supply of crocins is insufficient to meet current demand. The biosynthetic pathways for

• cell suspension culture, heterologous biosynthesis, and total synthesis [16][17]. Crocins can be obtained from plant cell culture, but the production is prone to epigenetic silencing and toxic intermediates. The chemical synthesis of crocins is challenging due to the presence of numerous chiral centers

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• macrocyclizations (Scheme 1c). NAC thioester and other related mimics (such as coenzyme A (CoA), phosphopantetheine, and thiophenol) span the gap between the chemical synthesis and biosynthesis languages and expand the substrate promiscuity of TE domains. This bridge makes the in vitro TE-catalyzed macrocyclization

• contrast to Kang’s chemical synthesis route, this biotransformation provided a more efficient and productive strategy for the desoaminylation of macrolide aglycones. Combining in vitro and in vivo enzymatic reactions together, this chemoenzymatic platform exhibits the potential to access a broader range of

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• of 4-azido-6,7-dimethoxy-2-sulfonylquinazoline derivatives 12 were proven by chemical synthesis of the regioisomers 15 (Scheme 7) and X-ray analysis of 12a (Scheme 6). 6,7-Dimethoxy-2,4-diazidoquinazoline (13) was synthesized from commercially available dichloroquinazoline 7 in 93% yield. Further

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• for 6000 years [1]. Initially, indigo has been extracted from the plant species, for example Indigofera tinctoria and Polygonum tinctorium in Asia and America, Isatis tinctoria or dyer’s woad in Europe [2] before the chemical synthesis of indigo was achieved by the German chemist Adolf von Baeyer [3

• ]. As an alternative to the chemical synthesis of indigo, environmentally friendly biological approaches towards constructing the indigo scaffold are also being developed for nearly a century [5][6][7][8]. The biosynthetic methods include production of indigo by microorganisms and enzymatic synthesis

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• bacteria. Accessing this valuable cell wall precursor is important both for studying cell wall synthesis and for studying/identifying novel antimicrobial compounds. Herein, we describe optimizations to the modular chemical synthesis of lipid II and unnatural analogues. In particular, the glycosylation step

• ramoplanin [2]. It is also the target for a host of other antimicrobials (mostly non-ribosomal peptides), including the tridecaptins [3], nisin [4], teixobactin [5], clovibactin [6], malacidin [7], and cilagicin [8]. Despite significant progress in the chemical synthesis of lipid II and its analogues, the

• , the chemical, chemoenzymatic, or biochemical synthesis of lipid II and its variants has been achieved by several research groups [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Nonetheless, considering the current state of knowledge, the chemical synthesis approach emerges as

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• ligation from shorter 20 to 60 nt ODNs produced by automated de novo chemical synthesis. While these methods have made many projects in areas such as synthetic biology and protein engineering possible, they have various drawbacks. For example, they cannot produce genes and genomes with long repeats and

• have difficulty to produce sequences containing stable secondary structures. Here, we report a direct de novo chemical synthesis of 400 nt ODNs, and their isolation from the complex reaction mixture using the catching-by-polymerization (CBP) method. To determine the authenticity of the ODNs, 399 and

• to address all the aforementioned problems, such as generating sequences having highly stable secondary structures [18]. In this paper, we report a method to access long ODNs involving automated direct de novo chemical synthesis and isolation of full-length sequences using the catching-by

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

• requires a multistep process in conventional chemical synthesis [39][40][41]. Among the various widely available and abundant substrates for photocatalyzed reactions, natural and unnatural α-amino acids play a very important role, given their paramount importance across several chemistry fields as well as

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• solubility in water. Among exceptional properties belongs to easy post-transformation of acylimidazoles to common carbonyl analogs. These tunable properties allow the use of acylimidazoles in chemical biology research, which includes chemical synthesis of proteins/peptides, structure analysis, and functional

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• , e.g., the antiplatelet drug clopidogrel [7] or the β-lactam antibiotic amoxicillin [8] (Figure 1). Therefore, the chemical synthesis of α-aryglycines has received considerable attention. Among the different methods introduced over time, multicomponent reactions utilizing an in situ generated reactive

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• chemical synthesis of macrocyclic lactones which are the key structural motifs in some biologically active compounds, 14-methyl-2-phenoxy-1-oxa-2-phosphacyclotetradecane 2-oxide (74) was synthesized as the hapten from phenyl hydrogen (12-hydroxytridecyl)phosphonate (73) via Mitsunobu reaction. The

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• mixtures of the desired and undesired positional alkene isomer could be obtained. We believe an outstanding challenge in the field of chemical synthesis is to find mild and catalytic deprotection chemistries for dithiane-type systems, be they reductive, hydrolytic or oxidative. In particular, a more

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• and diverse functionalization of the isocoumarin products highlight the tremendous synthetic potential of this methodology in chemical synthesis and drug discovery. Experimental A 10 mL screw-cap vial was charged with enaminone 1 (0.2 mmol), iodonium ylide 2 (0.6 mmol), [Cp*RhCl2]2 (6.2 mg, 5 mol

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

• chemoselective manner [3]. The development of persistent radicals [4] as synthons in chemical synthesis, coupled with the advancements in generating and manipulating transient radicals [5] as cross-coupling partners in an array of chemical reactions, gives access to a wide variety of “new” retrosynthetic

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• Petri A. Turhanen University of Eastern Finland, School of Pharmacy, Biocenter Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland 10.3762/bjoc.18.153 Abstract The chemical synthesis of the dideuterium-labelled ATP analogue 1-adenosin-5’-yl-3-(3-methylbut-3-en-1,1-d2-1-ol) triphosphoric acid

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• chemical synthesis [1][2]. Within this period, the Beilstein Journal of Organic Chemistry has organized two Thematic Issues (i.e., Mechanochemistry and Mechanochemistry II) to facilitate the open dissemination of the best research in the field of synthetic organic mechanochemistry. The great success of

• activation to advance chemical synthesis on various fronts. Therefore, we hope you enjoy reading the variety of manuscripts in this Thematic Issues as much as we enjoyed editing it, which was only possible thanks to the impeccable assistance by the Editorial Team of the Beilstein-Institut. Lars Borchardt and

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• , including traditional isolation from nature [5][6][7][8] and chemical synthesis [9], have been made to expand the structural diversity of FC-type diterpenoids for drug development. Along with the development of low-cost sequencing technologies and tractable heterologous expression systems, genome mining has

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• Chemical synthesis of 6-chloro-6-deoxy- and 6-amino-6-deoxy-mannose 1-phosphates We first required access to appropriate glycosyl 1-phosphates (as putative substrates for enzymatic pyrophosphorylative coupling) to then access the sugar nucleotide GMD probes of type 8 and 9 (Figure 1c). Accordingly

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• in part due to their usefulness in medicinal chemistry [278] and research to reach even more elaborated amines is warranted. Concerning natural product synthesis, which has been the main source of chemical synthesis challenges in the last century, Paul Wender’s approach consisting in also reaching

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

• likely is the most pragmatic and straightforward preparation of the enzymes for their use in chemical synthesis. The assay setup used for all PPKs is similar to established ATP regeneration systems with PPK2 enzymes, with a 10:1 excess of polyP (calculated as single phosphates [49]) over the nucleotide

Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides

• Md Azadur Rahman,
• Kana Kuroda,
• Hirofumi Endo,
• Norihiko Sasaki,
• Tomoaki Hamada,
• Hiraku Sakai and
• Toshiki Nokami

Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117

• one of a few examples of chemical synthesis of chitin oligosaccharides through polyglycosylation of a glucosamine monosaccharide [6]. Recently, we have reported electrochemical polyglycosylation using a glucosamine derivative as a monomer [7]. This is another example of polyglycosylation of a

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• Originally, musk was obtained from the gland of the musk deer and used as a powerful base note. Due to the high price of musks of natural origin, the vast majority of them is produced by chemical synthesis. Today, a plethora of synthetic musks with a broad structural and olfactory diversity are available

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• the reduction of the environmental effects of chemical synthesis [22]. The use of ultrasonic irradiation allows for optimal mixing of the reactants and the catalyst by enhancing the homogeneity of the reaction medium. It also decreases the chance of agglomeration of the heterogeneous nanoparticles

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

• -homoarabinofuranosyl nucleosides 9a,b. Chemical synthesis of nucleosides 9a,b starting from diacetone ᴅ-glucofuranose. a) Plausible mechanism for the synthesis of (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabinofuranosyl nucleosides 9a,b from 16a,b and b) intermediates detected on the basis of mass

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• proposed mechanism for the cyanation step is depicted in Scheme 21. Chemical synthesis usually needs labor-intensive and tiresome procedures. One of the approaches to overcome these challenges is to perform the reactions in flow [44]. The major advantages of this approach include predictable reaction scale