Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• substituted saccharides. The vast diversity among CEs is organized into 16 different families [123]. Members of the CE6 family are typical serine-type esterases. A cold-adapted CE6 enzyme, CEST, was cloned and expressed in E. coli from Microbulbifer thermotolerans DAU221 with a temperature optimum of 15 °C

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• purposes [1][2][3][4][5][6]. Isonitrile-based multicomponent reactions, such as the Groebke–Blackburn–Bienaymé (GBB) reaction, is an important tool in chemical synthesis providing easy access to a huge compound diversity and complexity [7][8][9][10][11][12][13][14][15][16][17]. Essentially, the GBB

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• N–H bond was the most stable conformer, allowing for an intramolecular F∙∙∙H hydrogen bond. However, 3-fluoropyrrolidine displayed extensive conformational diversity (ΔG0 among conformers ≤1.6 kcal⋅mol−1) as the intramolecular interactions were not sufficiently stabilizing to dictate a dominant

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• (HMM) for split burpitide precursor peptides. Using this approach, we assembled 700 transcriptomes and used predicted precursor peptide diversity for target discovery of new cyclopeptide alkaloids. Additionally, metabolomic analysis revealed the tissue distribution of these molecules across select

• peptides for split burpitide pathways, we developed a custom HMM (see Supporting Information File 1, Figure S1). This approach gave us the speed, sensitivity, and customization needed to identify diverse sequences. We targeted a diversity of plants from every available order in Streptophyta for a total of

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• by harsh reaction conditions, which reduces functional group compatibility and product diversity. As such, the development of practical methods for the preparation of alkylnitriles from readily available starting materials are particularly valuable in synthetic and medicinal applications [15][16][17

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• of diversity-oriented synthesis of N-heterocycles via sequential multicomponent approaches, we envisioned that α-aminoacetals could act as bifunctional building blocks along with 1,2-diaza-1,3-diene (DD) coupling partners [22][23], in obtaining functionalized N-aminohydrazones as key intermediates

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• , we highlight the reputation of this reaction approach to access number and scaffold diversity of a library of isatin-based α-acetamide carboxamide oxindole hybrids, promising anticancer agents, in a mild and fast sustainable reaction process. The library was tested against six human solid tumor cell

• with remarkable atom economy, cost and time-effective and mainly diminishing waste production is a conscientious boost for structural diversity and sustainability [1][2][3]. The well-known Passerini, Ugi, Mannich, Biginelli, Hantzsch and Strecker reactions are some examples of the classic MCRs

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• were installed in an outward-radiated manner, which expands the structural diversity to exploit the chemistry at the periphery of [n]CMP (Figure 1b). Through the use of Suzuki–Miyaura coupling for macrocyclisation, pyridinyl and phenylene rings were assembled in an alternating fashion, which afforded

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China 10.3762/bjoc.20.86 Abstract Terpenoids are one of the largest class of natural products with diverse structures and activities. This enormous diversity is embedded in enzymes called terpene synthases (TSs), which

• -methyltransferases, or engineered lepidopteran mevalonate pathways. The substrate promiscuity of TSs not only expands the structural diversity of terpenes but also highlights their potential for the discovery of novel terpenoids via combinatorial biosynthesis. In this review, we focus on the current knowledge on

• broad range of bioactivities [2][3]. Despite their stunning diversity, all terpenes are biosynthetically derived from two general isomeric C5 building blocks, dimethylallyl diphosphate (DMAPP, 1) and isopentenyl diphosphate (IPP, 2), via the mevalonate (MVA) or methylerythritol 4-phosphate (MEP

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

• of the de novo approach and furthermore provides an extra efficiency, complexity and diversity in the same number of steps (Figure S1, Supporting Information File 1). Also, it offers a flexibility of placement of the tetrazole moiety in the scaffold and enables additional facile post-modifications

• envisioned the use of multicomponent reactions in both steps. The use of MCRs provides the benefits of simplicity, speed, complexity, and diversity with the minimum number of steps and with an environmentally friendly nature. First, we focused on the use of the Passerini-tetrazole reaction for the synthesis

• pathways in terms of economy, sustainability, generalizability, step-count, reaction simplicity, and yields. With these tetrazole building blocks in hand, we next aimed to investigate the scope and limitations by assembling smaller compound libraries with a high degree of complexity and skeletal diversity

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• herein an enantioselective palladium-catalyzed Heck–Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-1H-pyrroles with aryldiazonium salts, using the chiral N,N-ligand (S)-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• cyclization mechanism of spiroviolene. Keywords: boron migration; diterpene; spiroviolene; stereochemistry; Introduction Terpenes represent one of the most fascinating families of natural products due to their structural complexity and diversity, as well as their indispensable biological functions that

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• the low yield of 3al. We subsequently turned our attention to explore the effect of structural diversity of the ortho-ester-substituted diaryliodonium salts. Firstly, a family of substituted diaryliodonium salts were synthesized in a one-pot procedure. These ortho-substituted diaryliodonium salts were

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• analogs. This discovery not only broadens the known chemical diversity of DMTs from bacteria, but also provides new insights into DMT biosynthesis in bacteria. Keywords: bacterial terpenoid; cytochrome P450s; drimane-type sesquiterpenoid; Streptomyces clavuligerus; terpenoid biosynthesis; Introduction

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

• polyketides; thioesterase; Introduction Nonribosomal peptides, polyketides, and their hybrids exhibit significant diversity and a broad spectrum of bioactivities [1][2][3]. Particularly, macrocycles from these three categories of natural products are vital resources for developing pharmaceuticals and drug

• responsible for the structural diversity of natural products, both NRPS and PKS contain thioesterase (TE) domains in the final elongation module, which contribute to terminating biosynthesis [13][14]. Typically, TE domains cleave the thioester bond between the last PCP or ACP domain and the intermediate of

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• of TCs in fungi. Keywords: diterpenoids; fungi; genome mining; labdane; terpene cyclase; Introduction Terpenoids are a structurally diverse family of natural products, including more than 80,000 compounds [1]. In the biosynthesis of terpenoids, terpene cyclases (TCs) add structural diversity and

• stereoisomers, ent-CPP and syn-CPP. Class II TCs can also generate further structural diversity through hydride shifts, methyl shifts, and/or skeletal rearrangement of the labdadienyl+ diphosphate intermediate which is formed by the initial bicyclization. Following this class II TC-mediated cyclization, class I

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

• . Diversity and yields for 2-amino-4-azido-6,7-dimethoxyquinazolines 17. Supporting Information Supporting Information File 58: Experimental, copies of spectra and crystal data, data collection and structure refinement details for compound 12a. Supporting Information File 59: Checkcif for compound 12a

Organic electron transport materials

• Joseph Cameron and
• Peter J. Skabara

Beilstein J. Org. Chem. 2024, 20, 672–674, doi:10.3762/bjoc.20.60

• functionalities such as cyano groups [1]. This is one of the key advantages of organic electron transport materials compared with inorganic materials – the molecular structures can be easily tuned to achieve desired characteristics. The diversity of materials used as electron transport layers is also an advantage

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• this compound class is derived from the aromatic precursor 3,5-dimethylorsellinic acid (DMOA). In this study, we constructed engineered metabolic pathways in the fungus Aspergillus oryzae to expand the molecular diversity of meroterpenoids. We employed the 5-methylorsellinic acid (5-MOA) synthase FncE

• pathway; their non-terpenoid portions can be polyketides, indole, or shikimate-derived compounds [1][2][3]. Their hybrid nature significantly contributes to their structural diversity and wide range of biological activities. Although meroterpenoids are found ubiquitously in nature, as both primary and

• meroterpenoids, we can access meroterpenoids that have not yet been reported. In this study, we aimed to expand the structural diversity of meroterpenoids through artificial pathway construction. To achieve this, we constructed a series of artificial metabolic pathways by harnessing genes from the funiculolide

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• Zhiyang Quan Takayoshi Awakawa RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan 10.3762/bjoc.20.50 Abstract Meroterpenoids are hybrid compounds that are partially derived from terpenoids. This group of natural products displays large structural diversity, and many

• mutagenesis of key enzymes, including terpene cyclases and α-ketoglutarate (αKG)-dependent dioxygenases, that contribute to the structural diversity. Notable progress in genome sequencing has led to the discovery of many novel genes encoding these enzymes, while continued efforts in X-ray crystallographic

• of acyl-CoA: cholesterol acyltransferase [4]. In this mini-review, we focus on the fungal meroterpenoids biosynthesis, especially terpenonid cyclizations and post-cyclization modifications, which mostly contribute to the skeletal diversity. Several terpenoid cyclases and αKG-dependent dioxygenases

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• with emphasis on the structural diversity of small-molecule ligands. In this context, acyl-acyl carrier protein (acyl-ACP) thioesterase inhibitors have shown a remarkable variability. Fatty acid thioesterase (FAT) enzymes represent a family of proteins exclusively found in higher plants. They mediate

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• -rich fluid emissions and unique sulfur oxidation–reduction reactions [1]. Due to the unique habitat, microorganisms surviving in the deep-sea cold seeps may serve as promising sources of secondary metabolites with functional and structural diversity [2]. In particular, two indole diketopiperazine

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• one of the most extensively used, owing to their structural diversity and widespread commercial availability [18][19]. Carboxylic acids 1 can generate radicals under oxidative conditions, as in classical decarboxylative halogenation reactions (Hunsdiecker reaction) that proceed via a radical mechanism

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• Glycomics (NCFG, Figure 2a) and the Glycosciences Laboratory at Imperial College London (ICL, Figure 2b). We note that, together, this encompasses 1,046 unique glycan sequences, spanning all major glycan classes and substantial taxonomic diversity. Next to these unique sequences, even more effects stem from