Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• completed through bridging from the exomethylene group, and (iii) the annulation from the exomethylene group proceeds in a barrier-free manner. Keywords: biosynthesis; carbocation; cation–π interaction; DFT; terpene; Introduction Terpene/terpenoids are most abundant natural products in nature, more than

Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an alkynylation–cyclization–iodination–alkylation sequence

• Nadia Ledermann,
• Alae-Eddine Moubsit and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2023, 19, 1379–1385, doi:10.3762/bjoc.19.99

• state, in good yield. Keywords: alkynylation; catalysis; cyclization; indoles; iodination; multicomponent reactions; Introduction Indoles and their derived substitution patterns are omnipresent heterocyclic structural motifs in nature [1], many natural products [2][3], drugs [4][5][6][7][8], and dyes

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• ; Introduction Acyloins (also known as α-hydroxy ketones) are widely found as structural motif in natural products [1][2][3][4][5][6][7] and bioactive molecules [8][9][10][11] (Figure 1). They can also be used as building blocks in organic synthesis [12][13][14], involved in numerous transformations to other

• column chromatography to give the coupling product 3. Selected natural products and pharmaceuticals bearing acyloins. Proposed reaction mechanism. Strategies for the synthesis of α-trifluoromethyl acyloins. Substrate scope. Standard conditions: a solution of alkyl carboxylic acid 1 (0.4 mmol), 2 (0.6

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• are widespread as essential building blocks in various drugs, natural products, agrochemicals, and materials. Modern economy requires developing green strategies with improved efficiency and reduction of waste. Due to its atom and step-economy, the cross-dehydrogenative coupling (CDC) reaction has

• synthesis of compounds with quaternary centers and natural products with high structural complexity. In 2014, Li et al. reported a CuCl2-catalyzed cross-dehydrogenation coupling reaction of C(sp3)–H bonds adjacent to an ether oxygen and the C(sp3)–H bonds at the α-position of a carbonyl functionality in the

• tricyclic chromane nucleus from 8-hydroxyisochromanes and 1,3-dicarbonyl compounds in the presence of Cu(OTf)2 and T+BF4− (Scheme 7b) [57]. The strategy has a wide range of applications and is highly diastereoselective, making it an attractive strategy for synthesizing related natural products. The role of

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• ylide; sustainable; Introduction Arylamines are among the most privileged structural motifs appearing in various natural products, and bioactive molecules [1][2] as well as offer widespread applications in pharmaceuticals, agrochemicals, dyes, and materials science [3][4]. Particularly the

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• acyclic, carbocyclic, heterocyclic, and polycyclic molecular architectures with high molecular complexity. In particular, asymmetric organocatalysis plays a pivotal role in the construction of optically active, bioactive, and natural products. The main advantages of organocatalyzed stereoselective

• mechanistic approaches with explanation about the origin of stereoselectivities has also been elaborated. This reaction has been successfully utilized as the key step in the syntheses of different important natural products which have been included in this article as well. On searching the literature, it has

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• is an important aromatic heterocyclic scaffold found in many natural products and predominantly used in pharmaceuticals. Continuous efforts are being made to design and synthesize various pyrrole derivatives using different synthetic procedures. Among them, the Clauson–Kaas reaction is a very old and

• many natural products [1][2][3] and biologically active molecules [4][5][6][7]. Pyrroles are a significant class of five-membered aromatic nitrogen-containing heterocyclic skeletons that have attracted much attention due to their broad spectrum of biological activity, such as anticancer [8][9][10

• pharmaceutically active molecules, polymer synthesis, total synthesis of natural products, porphyrin functionalization, and the synthesis of various pyrrole-containing heterocyclic molecules. We believe that this review will be useful and will encourage researchers to apply the modified Clauson–Kaas reaction to

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

• ground state catalyst [21][22][23][24][25][26]. While early research has focused on methods for the functionalization of relatively simple hydrocarbons [27][28][29][30], developments in photoredox catalysis have gained traction recently as a viable strategy for the total synthesis of natural products [31

• position via a sequential electron transfer–proton transfer (ET/PT) [52][53][54][55][56][57][58][59]. With our ongoing interest of establishing new methods for the asymmetric synthesis of nonproteinogenic tryptophan derivatives as well as their associated indole alkaloid natural products [60][61][62][63

• common synthetic route to ergot alkaloids, providing an advantageous synthetic method for this class of natural products. Further studies on the utility of the decarboxylative radical cyclization and their applications are currently being investigated in our laboratory. (a) Transformations of DMAT to

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• recently identified as an untapped reservoir of novel natural products [15]. In particular, the strain Massilia sp. NR 4-1 was subject of several chemical investigations. In these studies, the bacterium was demonstrated to produce a diverse array of secondary metabolites, namely the pigment violacein [16

• ]. Natural products that are structurally related to 1–6 were discovered in Pseudomonas aeruginosa. It was shown that these compounds function as signaling molecules involved in quorum sensing and stress response [24] which might be an explanation for their low bioactivity against the tested bacteria. Upon

• ] and the photoxenobactins [32]. A unifying theme in the biosynthesis of these natural products is the use of a thiotemplate-based assembly strategy [33]. The molecular building blocks that are needed for the biosynthesis are covalently bound via thioester bonds to multi-domain enzymes. The domains

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

• its applications in the total syntheses of complex natural products and other molecules of biological relevance [13][14]. Acylimidazoles proved to be versatile building blocks broadly applicable in asymmetric catalysis and organic synthesis. Today, acylimidazoles are used as ester/amide surrogates

• control of RNA [16]. Moreover, Campagne and co-workers showed that Cu–NHC-catalyzed conjugate additions of dialkylzinc reagents proceed with high enantioselectivities [17][18][19]. Furthermore, this methodology allows iterative access to 1,3-disubstituted motifs that are present in various natural

• products [20]. A salient feature of conjugate additions of organometallic reagents is that they generate reactive metal enolates as primary products. These enolates can be used in a variety of subsequent transformations [21]. Chiral enolates generated by conjugate additions react with carbonyl compounds

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• Haritha Sindhe Malladi Mounika Reddy Karthikeyan Rajkumar Akshay Kamble Amardeep Singh Anand Kumar Satyasheel Sharma Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research - Ahmedabad, Gandhinagar, Gujarat, 382355, India Department of Natural Products

• , National Institute of Pharmaceutical Education and Research - Ahmedabad, Gandhinagar, Gujarat, 382355, India 10.3762/bjoc.19.62 Abstract Pyridine is a crucial heterocyclic scaffold that is widely found in organic chemistry, medicines, natural products, and functional materials. In spite of the discovery

• the mechanisms involved. Keywords: C–H functionalization; heterocycles; pyridine; rare earth metal; transition-metal-catalyzed; Introduction Pyridine, one of the most important azaheterocyclic scaffolds, is found in a diverse range of bioactive natural products, pharmaceuticals, and functional

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• occurrence among natural products [1] and is a key structural component of several pharmaceuticals, agrochemicals, dyestuffs, and materials. Particularly, the well-known antimalarial alkaloid quinine isolated from Cinchona bark comprises a quinoline core (Figure 1a) [2]. Moreover, numerous quinoline

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• applications in various areas of science and technology [3][4][5]. For example, the use of photoreactions for the preparation of complex natural products allows reducing the number of synthetic steps [6][7][8][9]. Moreover, in some cases photochemical processes can open access to complicated multifunctional

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• be used as potential drug candidate against Alzheimer's disease [14]. Compounds containing the imidazo[1,2-a]pyridine moiety are present in many natural products and marketed drugs, e.g., alpidem (an anxiolytic) [15], necopidem (anxiolytic) [16], zolpidem (hypnotic for the treatment of insomnia) [17

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

• several well-known natural products with interesting biological properties, such as the glycopeptide antibiotics vancomycin and teicoplanin [5] or feglymycin [6], a 13mer peptide which contains nine α-arylglycines in its backbone. α-Arylglycine derivatives are used in the production of important drugs

• arylglycine-containing natural products. Currently, we are performing a detailed mechanistic study in order to overcome still existing limitations of the method and to provide a truly general approach to arylglycines with uniformly high yields and enantioselectivities. Biologically active molecules containing

• , sulfonamides and aryltrifluoroborates is described. This process provides modular access to the important α-arylglycine motif in moderate to good yields and enantioselectivies. The formed α-arylglycine products constitute useful building blocks for the synthesis of peptides or arylglycine-containing natural

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• dibenzo[b,f]heteropine template is an important feature in several commercial and lead active pharmaceutical ingredients, biologically active natural products, dyes in OLEDs and dye sensitive solar cells, and in certain ligands. This review provides an overview of the different synthetic strategies

• ). Selected pharmaceuticals with the dibenzo[b,f]azepine skeleton. Examples of 10,11-dihydrodibenzo[b,f]azepine-based ligands. The dibenzo[b,f]azepine moiety in dyes with properties suitable for the use in organic light emitting diodes and dye-sensitised solar cells. Selective bioactive natural products (13

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• moieties in several bioactive pharmaceuticals and natural products [1][2][3][4]. Moreover, due to their susceptibility towards 'exited-state intramolecular proton transfer' phenomena, IPs are also effective in optoelectronics and materials sciences [5][6]. C-3-functionalized imidazo[1,2-a]pyridines are

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• °16'51.5"N 100°43'30.3"E) in August 2021 and identified by Mr. Martin van de Bult, Doi Tung Development Project. A voucher specimen (UP-CNP003) was deposited at the Chemistry of Natural Products for Sustainability Laboratory, School of Science, University of Phayao. Extraction and isolation The fresh

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

•  44B). In the end, protonation of the Li enolate affords the spiroindane boronate. Due to their paramount role in the fields of bioactive natural products and medicinal chemistry, there is a growing interest in enantioenriched cyclobutanes. Recently, the group of Hall was engaged in developing

• addition to cyclohexenone 1, followed by the trapping of the Mg enolate with ethyl cyanoacetate (221). Consequent α-alkylation resulted in the multifunctionalized product 223 in 61% yield (Scheme 58). Natural products with complex multicyclic structures lacking functional groups (lack of oxygenation) are

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• ; Introduction Transannular cycloaddition reactions (TCRs) are useful for the synthesis of complex natural products and other biologically active compounds with high efficiency and stereoselectivity [1][2][3][4]. There are several different ways in which TCRs can occur, depending on the nature of the starting

Total synthesis: an enabling science

• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 474–476, doi:10.3762/bjoc.19.36

• Bastien Nay Laboratoire de Synthèse Organique, École Polytechnique, CNRS, ENSTA, Institut Polytechnique de Paris, 91128 Palaiseau, France 10.3762/bjoc.19.36 Keywords: chemical complexity; natural products; synthetic methodologies; total synthesis; Total synthesis is a topic strongly related to

• " (edited by D. Chen and D. Ma) [1] or "Natural products in synthesis and biosynthesis" (edited twice by J. Dickschat) [2][3]. Previously, the early thematic issue "Indolizidines and quinolizidines: natural products and beyond" (edited by J. P. Michael) from 2007 [4] displayed some of the very first total

• constantly needed to improve methods and strategy, keeping in mind the difficulty of performing transformations on highly functionalized compounds, the total synthesis of complex natural products is indeed mature in terms of efficiency, practicality, economy, and scalability. In short, it has become an

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• late-stage functionalization strategy [51][52][53] for the synthesis of natural products [42][54][55][56][57][58][59]. The goal of this review is to highlight and discuss the recent approaches for the synthesis of fluorinated derivatives by the direct incorporation of a fluorinated group of XRF type

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• the natural products. Keywords: allylation; aldol reaction; latrunculins; stereocontrol; total synthesis; Introduction Latrunculins constitute a class of marine polyketide natural products isolated from Sponges like Negombata (= Latrunculia) magnifica [1][2]. They are characterized by the presence

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

• quantities for the evaluation of biological/pharmacological activities. Review 1 Isolation 1.1 Isolation of combretastatins D series Combretastatins comprise a large family of structurally diverse natural products divided into the “A” (cis-stilbenes), “B” (dehydrostilbenes), “C” (phenanthrenes), and “D