A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• -type syntheses, MCRs have become helpful tools for more efficient preparation of chemical libraries with higher molecular diversity and complexity in fewer steps and less time [28][29]. Considering the limitations of existing methods, as well as the applications of 5-aryldeazaalloxazines 2, and in the

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• . [15][18]. Further, the application of reagents with additional functional groups in the Ugi reaction makes it possible to further increase the complexity of the product structures, also due to possible post-transformation reactions. For example, if an unsaturated bond is present in the aldehyde

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• enzymes to synthetic intermediates, the chemo-enzymatic total synthesis of chalcomoracin (3) was comprehensively illustrated (Scheme 5 and Scheme 6). The biosynthetic pathway of natural products in plants still remains challenging due to the complexity and redundancy of their genes, making it difficult to

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• resulting natural products with a spectrum of chemical complexity, contributing to the broad range of biological activities exhibited by RiPPs. Bioactivities attributed to RiPPs include a wide range of effects, such as antibiotic, antifungal, antiviral, antiparasitic, antitumour, analgesic, anti

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• . As molecular complexity increases, this task becomes more challenging. This paper introduces pKalculator, a quantum chemistry (QM)-based workflow for automatic computations of C–H pKa values, which is used to generate a training dataset for a machine learning (ML) model. The QM workflow is

• value. This is slightly different from our previous approach. However, because of the higher complexity of the reaction and the similarity of aromatic C–H sites, we purposely allow the QM workflow and the ML model to assess more sites as ‘1’ or true site. When the pKa value is within 1.5 pKa units, we

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

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• the halogen bonds (Scheme 5). We used Bader’s quantum theory of atoms in molecules (QTAIM) [41] and assessed ρ(r), ∇2(r), and associated values. However, to minimize complexity we elected to focus on the distance between the bond critical points (BCP) and the atomic centers (available in Supporting

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

• preparation by using small building blocks and that lead, through appropriate transformations, to a product that becomes a substrate for another complexity-generating reaction, merit investigation [13][14][15]. Herein, we report a 3-CR-based synthesis of new properly decorated (thio)hydantoin framework able

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• of handling, and versatile reactivity, etc. render these catalysts highly attractive for adoption in organic synthesis. In particular, the field of olefin difunctionalization, known for its rapid assembly of molecular complexity, has been a fertile ground for innovation for hypervalent iodine

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• potentially useful molecules. Keywords: Cannizzaro reaction; crossed-Cannizzaro; desymmetrization; Lewis acid catalyst; natural products; Introduction The synthesis of functionalized molecules with structural complexity has always been a challenge to synthetic chemists. The Cannizzaro reaction, in its

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• generally attributed of diaryl selenoxides such as compound 8 [39]. Despite the complexity, we could confirm the [M + H]+ ions of the isomeric monoselenides 4 and 5 from HRMS data (Figure S10, Supporting Information File 1). In addition to the above mentioned (possible) organoselenium compounds, the oxamide

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

• chemists regarding process formation of new bonds and synthesis of new scaffolds. In drug discovery and development, medicinal chemists struggle everyday towards the creation of new synthetic methods, driven by the increasing complexity of the molecules and taking into consideration economic and social

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• (GPP, FPP, GGPP) undergo highly complex cyclisation cascades forming terpenes and terpenoids that often have great structural complexity. For class I terpene synthases this multistep process is initiated by a heterolytic C–O bond cleavage, separating the diphosphate and isoprenoid ion pairs [3][4]. The

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

• efficient synthetic accessibility of drug-like molecules is of key importance. Interestingly, over the years the complexity of molecules entering the market is steadily increasing, supposedly due to the increasing complexity of contemporary molecular targets. A major Swiss API CRO reported that the

• 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

• 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

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

• complexity in a synthetic route. The palladium-catalyzed coupling of arenediazonium salts with olefins, the Heck–Matsuda reaction, has been instrumental in this strategy involving the desymmetrization of cyclic systems [3], especially five-membered substrates [4][5][6][7]. As we have demonstrated previously

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

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

• pikromycin and the aglycones in this family, 10-deoxymethynolide (24) and norbonolide (25), using asymmetric aldol reaction, Yamaguchi esterification, and ring-closing metathesis as key steps [65][66]. Nevertheless, the inherent complexity of these natural products demands high step counts, leading to low

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

• complexity. TCs are generally classified into two main classes, class I and class II. Class I TCs initiate the cyclization by heterolytic cleavage of substrates to generate a diphosphate anion and an allylic carbocation, and class II enzymes start cyclization by protonating a double bond or an epoxide

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• , greatly increasing the molecular complexity of the starting substrate. Using radical chemistry would lead to a regioselective addition of azide radicals to the alkene, forming selectively the most stabilized C-centered radical. A prominent method for the generation of azide radicals relies on hypervalent

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

• strong inosine 5-monophosphate dehydrogenase inhibitor [6]. The biosynthesis of fungal meroterpenoids has garnered interest in the organic chemistry field due to their structural complexity and associated intriguing enzymatic reactions and has thus been extensively researched for over a decade, providing

Introduction of a human- and keyboard-friendly N-glycan nomenclature

• Friedrich Altmann,
• Johannes Helm,
• Martin Pabst and
• Johannes Stadlmann

Beilstein J. Org. Chem. 2024, 20, 607–620, doi:10.3762/bjoc.20.53

• an ultimate solution to this dilemma as we think it is not yet time to impose another layer of complexity onto the herein proposed model. On top, automatic converters will encounter difficulties with such side rules. Nevertheless, for “domestic needs” shall four options be presented (Scheme 1

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

• that no new atoms are introduced into the molecule, thus ensuring first-order kinetics of the process without complexity. One of the possible mechanisms of redox-induced switching involves an intramolecular bond formation that introduces non-covalent interactions between tweezers endpoints leading to a

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• solvent and anion effects add complexity to mechanistic interpretation, and the reluctance of alkylgold complexes to undergo protodeauration under similar conditions give us pause [28]. While computational studies support protodeauration, the significantly lower reactivity of alkenes compared to alkynes

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

• reaction classes, we discuss the utility of the NHPI esters, with an eye towards their continued development in complexity-generating transformations. Keywords: decarboxylative couplings; mechanisms; NHPI-esters; radical reactions; Introduction The historical challenges of using radicals in synthetic

• stoichiometric electron donors, the presence of a TM catalyst, the formation of a charge-transfer complex, and the overall reaction conditions. While we hope that this discussion will spur the continued development of NHPI esters in complexity-generating transformations, it is not comprehensive, and we refer

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• atom efficiency, step and pot economies, decreased number of purification steps, or protecting-group-free synthesis. Multi-step domino [1][2] and one-pot [3] reactions represent a new powerful toolbox in organic synthesis to install molecular complexity economically and sustainably, starting from