Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• peroxides, oxaziridines, and their derived species are often applied as terminal oxidants [7][8]. The weakness of the O–O bond allows alkoxy radicals to form through homolysis or reduction [9]. The generated alkoxy radicals provide an accessible tool for selective radical cascades, where a variety of

• pioneer studies devoted to organic peroxide synthesis using radical cascades were reported by Kharasch [24][25]. In recent decades, there has been an intensive growth of publications in this field due to the integration of traditional peroxide chemistry with modern advances in organo-, metal- and

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• entirely cancelled by antioxidative pretreatment and cancer cell viability and proliferation were fully regenerated. Complete activation of cascades of caspases-3, -4, -6, -7, -8, and -9, loss of mitochondrial membrane potential, activation of proapoptotic PKCδ (protein kinase C delta), and inhibition of

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

• /ketalization cascades of generated (S)-34 proceeded predominantly, achieving the chemoenzymatic total synthesis of trichodimerol (2) in 27% yield from 33. In contrast, the use of acetone as the co-solvent resulted in the homodimerization of (S)-34 via Diels–Alder reaction between the cyclohexadienone moieties

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

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

• generate diverse terpene skeletons via sophisticated cyclization cascades. In addition to the many highly selective TSs, there are many promiscuous TSs that accept multiple prenyl substrates, or even noncanonical ones, with 6, 7, 8, 11, and 16 carbon atoms, synthesized via chemical approaches, C

• they often synthesize multiple products from a single substrate through complex cyclization cascades [4][5][6][7][8][9][10]. Based on the mechanism of initial carbocation generation, TSs generally fall into two main classes. Class I TSs generate an allylic cation from a prenyl substrate by

• . Classically, these prenyl analogs have been used as co-crystallization ligands [38], inhibitors of specific TSs [39], and tools to study the reaction mechanisms of cyclization cascades [40][41] which have been comprehensively addressed in important previous reviews [8][13]. Currently, noncanonical prenyl

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

• review summarizes recent advances in combining thioesterase-catalyzed macrocyclization and typical chemical approaches in the rapid generation of these complex cyclic natural products and their analogs with exquisite biological activity. Moreover, multistep enzyme cascades simplify synthesis by reducing

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

• triggers the next, which in the end yields a complex product. In contrast to a conventional “stop-and-go” method, only a single workup and purification is needed (Figure 1b), and therefore these reaction cascades can be considered superior to stepwise synthetic approaches in the context of green chemistry

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• /cyclization cascades from acrylamides for the synthesis of oxindoles [39][40][41]. The radicals are typically generated from alkyl halides [42][43][44], carboxylic acids [45][46][47], simple alkanes [48], alkylboronic acids [49], isocyanides [50], or other [51][52][53]. In this context, the group of Fu

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

• review highlights recent total syntheses that incorporate the best of both worlds. Keywords: biomimetic synthesis; cascades; common scaffold; hydrogen atom transfer; photoredox catalysis; Introduction Societal needs push sciences into new directions, as the urge for new pharmaceutical leads grows, in

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• the capacity of CYPs to catalyse unique enzymatic cascades. Limonoids are highly oxidised, modified and truncated triterpenoids; one of the most well-known limonoids is the eponymous compound limonin (18), which contributes to the bitter taste of citrus products (Figure 6C) [104]. The first steps of

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

• equilibrium. In fact, the authors observed an (compared to the adenosine-to-ATP cascades) increased yield of 80% cladribine triphosphate, with 2-Cl-dADP being the major byproduct [22]. The incomplete conversion (despite the irreversible reduction step) has been explained by the previously mentioned myokinase

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• ) [94]. Interestingly, the protocol used air as the oxidant, avoiding the use of stoichiometric oxidants like previous radical cyclization cascades. Generally, substrates with an electron-withdrawing group afforded the product in greater yield. The reaction proceeds through the formation of a sulfonyl

• synthesis of 3‐silylspiro[4,5]trienones 93 in good yield (Scheme 17) [95]. Compared to previously reported inter-/intramolecular CDC cascades, the authors were able to capture the post-cyclization aryl radical with the peroxide initiator rather than simply terminating the reaction with protonation. In terms

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

• transformations such as cyclizations or nucleophilic additions. Inspired by cationic terpene-type cyclization cascades, Jacobsen’s group turned their attention to the structure and properties of the chiral part of thiourea catalysts by introducing extended π-groups. A series of thiourea catalysts 53–55 with

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• hydroalkylation cascades. In 2016, the Cui group reported the hydroalkylation of olefins 59 using p-quinone methides 60 as electrophilic partners (Scheme 24A) [91]. Alkenyl alcohols could be employed without needing to protect the hydroxy functional group, and the acidity of the phenolic hydrogen present in the

• in Fe(III)-promoted hydroalkylation/cyclization cascades (Scheme 26A) [93]. Here, the carbocyclization occurred via a SN2 mechanism between the enolate intermediate and the tethered halide (Scheme 26B). Using arylidene diones 67 as radical acceptors, spiro compounds 69 were obtained in moderate to

• authors (Scheme 29). The latter steps of reductive coupling cascades of unactivated olefins with electron-deficient olefins under MHAT conditions involve the reduction of the radical generated at the α-position of an EWG to an enolate that could be engaged in further reactions (i.e., Scheme 23 to Scheme

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• a bound glutamate molecule [4]. Peptides often work as signaling molecules or hormones, such as small neuropetide endorphins, produced by the central nervous system to relieve stress or enhance pleasure. They produce signaling cascades in the brain by interacting with opiate receptors. Sometimes

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• diversity generates a rich collection of structures, all diversely able to trigger molecular cascades and to activate pathways, which also include adverse immunogenic responses. These events are inherently linked to the N-glycans’ 3D architecture and dynamics, which remain for the large part unresolved and

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• has been observed in many cases that exogenous substrates can be incorporated by bacteria into biosynthesis cascades of natural products. The use of substrates which lead to nonnatural derivatives of the natural product coined the field of mutasynthesis, e.g., siderophore analogue biosynthesis by P

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• tethered to cyclohexadienones that can be converted into complex polycycles by Ag-carbenoid-initiated cascades [16]. Recently, Zhu’s group developed a tandem 1,3‑dipolar cycloaddition/cyclopropanation silver-catalyzed reaction of enynals with alkenes [17]. In our previous studies, this silver carbene

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• -FDPs to sesquiterpenoids that may have applications in healthcare and agriculture. These results inform us of both the utility and limitations that non-natural functional groups have upon terpene cyclase-catalysed reaction cascades supporting the design of future biocatalytic syntheses. In particular

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• chemotypes of structurally complex products from a limited number of relatively simple starting materials just by varying the reaction conditions (temperature, solvent–catalyst system, activation method, forced realization of one of the cascades of multicomponent treatment). We decided to use this strategy

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• currently largely underinvestigated in the characterisation of TSs, even for cascades requiring its involvement. Structures of achiral terpenes: (E)-β-farnesene (1), α-humulene (2), 1,8-cineol (3) and sodorifen (4). A) Total ion chromatogram of a hexane extract from the incubation of FPP with BbS and B) EI

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• synthetic metabolic networks From above examples it becomes evident that for building completely novel pathways and/or complex reaction cascades, resources are required that provide synthetic biologists with the information to find individual enzymes for a given synthetic metabolic network. More than 116

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• , 117997, Russia 10.3762/bjoc.14.289 Abstract Phosphoribosyltransferases are the tools that allow the synthesis of nucleotide analogues using multi-enzymatic cascades. The recombinant adenine phosphoribosyltransferase (TthAPRT) and hypoxanthine phosphoribosyltransferase (TthHPRT) from Thermus thermophilus

• phosphoribosyltransferase; catalysis; enzyme; hypoxanthine phosphoribosyltransferase; multi-enzyme cascade; nucleotides; thermophiles; Introduction Bacterial phosphoribosyltransferases are used in multi-enzymatic cascades that perform nucleotide synthesis de novo [1][2]. Recently, we reported on the possibility of cascade

• corresponding nucleotides (Figure 1). The use of thermophilic phosphoribosyltransferases allows carrying out reactions at a higher temperature, so the concentrations of heterocyclic bases can be increased [1][2][3]. There is great interest in the development of multi-enzymatic cascades [4][5][6][7][8][9] for