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

• analogues 80 and 81 with shifted double bonds were synthesized to study the stereochemistry and cyclization mechanism of casbene synthase (CS) from the castor bean (Ricinus communis), which indicated a stereochemical course in accordance with the reported absolute configuration of casbene [41] (Figure 6b

• ). The same GGPP isomers (80, 81) were employed to generate novel diterpene derivatives and revealed the cyclization mechanisms of 12 di-TSs [48]. Similarly, dihydro-GGPP (82) and dihydro-GFPP (83) have been synthesized for biotransformation using several di- and sester-TSs. The conversion of analogues

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• yield in a ratio of 7:3. Indazole and its 4-bromo and 6-methoxycarbonyl analogues afforded the expected N1-alkenylated products 4ea–4ga in 43–68% yields. 1,2,3-Triazole and benzotriazole both smoothly participated in the reaction to give their respective products 4ha and 4ia in 60% and 81% yields

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• angle θ of 3-oxa-1,5-BCHs of roughly 80° is even larger than in 1,5-BCHs and is a significant deviation from ortho-benzenes. Like their hydrocarbon 1,5-BCH analogues, 3-oxa-1,5-BCHs (±)-74 can be accessed via an intramolecular [2 + 2] cycloaddition, and saponified to acids (±)-72 (Scheme 6A) [45

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

• findings from both the heterologous expression and substrate spectrum analysis indicate the particular affinity of CavA for the C-3 position, which might be used for chemoenzymatic synthesis of C-3 hydroxylated drimanyl meroterpenoids using drimenol and its analogues as substrates. However, it is important

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

• , demonstrating the effectiveness of our approach in the generation of structural analogues of meroterpenoids. Keywords: biosynthesis; meroterpenoids; natural products; pathway engineering; terpene cyclases; Introduction Meroterpenoids are a class of natural products partially biosynthesized from a terpenoid

• a general understanding of their biosynthesis [7][8]. Polyketide–terpenoid hybrids are among the largest families of meroterpenoids. Orsellinic acid, an aromatic polyketide, and its analogues have been commonly identified as polyketide components in fungal meroterpenoids. Notably, 3,5

• into distinct cyclized products (Figure 1C) [17][18][19]. In addition, a recent study has demonstrated that some of these transmembrane terpene cyclases can accept synthetic substrate analogues to yield several unnatural meroterpenoid molecules [20]. By mimicking nature’s strategy to synthesize diverse

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

• -crystal structure [12]. Additionally, greenhouse trials have shown that thiazolopyridine 5 and a large number of closely related analogues display excellent control of grass weed species in preemergence applications [13][14]. Independently, researchers at Syngenta have shown that the pyridine unit in the

• 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, i.e., 13a–c, and 7a–c, the acylated analogues 14a–c and 16a–f, as well as selected aminoboranes 17d and 17e, were tested for target affinity in dedicated in vitro tests, as well as for herbicidal effects in vivo upon preemergence application to plants. Based

• complete control of all tested weeds at an application rate of 320 g/ha, the corresponding 6-bromo analogues 13a–c showed higher sensitivity towards changes in the phenyl moiety. 6-Bromo-5-phenyl-2,3-dihydrothiazolo[4,5-b]pyridine (13a) showed only partial control of ALOMY and LOLRI, combined with moderate

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

• sulfur-containing ovalicin derivatives, along with three known analogues 3–5, were isolated and identified from the culture extract of Pseudallescheria boydii CS-793, a fungus obtained from the deep-sea cold seep sediments. Their structures were established by detailed interpretation of NMR spectroscopic

• . proliferatum with MIC values of 2, 4, and 4 μg/mL, respectively. Conclusion In conclusion, two new ovalicin sesquiterpenoid derivatives with a thioether bond, namely, pseudallenes A (1) and B (2), together with three known analogues 3–5, were isolated and identified from the cold seep-derived fungus P. boydii

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• triggered by thermal activation, photoirradiation and electron exchange as a powerful synthetic strategy to prepare a variety of π-CPCs. Review Contraction of 7-membered rings: chalcogen extrusion from heteropines The family of chalcogen heteropines, i.e., cycloheptatriene analogues incorporating one group

• -16 atom, have attracted attention from the chemists’ community since the 1950s, when the first syntheses of oxepine [37] and thiepine [38] were reported (Scheme 2). Analogues containing heavier atoms such as Se [39] and Te [40] appeared later in the literature. In relationship with its structure

• sulfur extrusion [44]. It appeared that thiepines carrying sterically demanding substituents on the sulfur α-positions as well as annelated analogues show substantially increased lifetimes, owing to steric and electronic effects [45]. With these criteria in mind, a variety of thermally-stable annelated

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

• -aminopyrazoles with azlactones under solvent-free conditions, through subsequent elimination of a benzamide molecule in a superbasic medium, is described by the Fisyuk group [13]. A further facile one-pot process toward a new series of copper(II) benzo[f]chromeno[2,3-h]quinoxalinoporphyrin analogues is described

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

• analogues through the incorporation of alternative building blocks at different stages of synthesis. Keywords: chemical glycosylation; lipid II; peptidoglycan; polyprenyls; total synthesis; Introduction Lipid II (Figure 1) is an essential bacterial glycolipid involved in peptidoglycan biosynthesis [1]. It

• 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

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• reaction is possible upon elimination of the resulting benzylic alcohol on D, allowing another arylation forming E [18]. This complex sequence of transformations is herein applied to the synthesis of 1-aryltetralines, analogues of cyclolignan natural products having important medicinal applications [19][20

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• linear azaacene structures but also non-linear structures as shown in Scheme 13. This versatility allowed for a broader range of conjugated molecules to be successfully prepared. The target azaacene analogues 62–64, featuring 2,6-(CH3)2C6H3 groups were obtained in yields ranging from 50 to 85% through a

• ]naphthylenes. Sequential Pd-catalyzed annulation reactions. Synthesis of biphenylene-containing unsymmetrical azaacenes 54a–c. Synthesis of biphenylene containing symmetrical azaacenes 58a,b. Synthesis of azaacene analogues 62–64. Synthesis of POA-type structure 69. Synthesis of boron-doped POA 73. Synthesis

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• -3 substitution in analogues of microbial behavioral modulators [54][56], prompted us to investigate a new synthetic approach that could provide a straightforward access to both 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides. Our approach falls within the broader methodological group of

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• more in-depth applications of fluoromethylated hydrazones and acylhydrazones to synthesize natural product analogues and fluorinated drugs is highly desirable. These methods should encourage the introduction of these difluoromethylated nitrogen-containing building blocks in future bioactives discovery

Benzoimidazolium-derived dimeric and hydride n-dopants for organic electron-transport materials: impact of substitution on structures, electrochemistry, and reactivity

• Swagat K. Mohapatra,
• Khaled Al Kurdi,
• Samik Jhulki,
• Georgii Bogdanov,
• John Bacsa,
• Maxwell Conte,
• Tatiana V. Timofeeva,
• Seth R. Marder and
• Stephen Barlow

Beilstein J. Org. Chem. 2023, 19, 1651–1663, doi:10.3762/bjoc.19.121

• . Their electrochemistry and reactivity were compared to those derived from 2-(4-(dimethylamino)phenyl)- (1b+) and 2-cyclohexylbenzo[d]imidazolium (1e+) salts. E(1+/1•) values for 2-aryl species are less reducing than for 2-alkyl analogues, i.e., the radicals are stabilized more by aryl groups than the

• , resulting in 1g• and 1h• being more reducing monomers than their non-methoxylated analogues 1b• and 1e•, respectively. Cyclic voltammograms of both 1H and 12 both reveal irreversible oxidations (with the corresponding 1+ reductions seen in subsequent reductive cycles, see Figure 6 for examples). These 1H

• example subsequent to processing. Conclusion In conclusion we have reported a number of new DMBI-H and (DMBI)2 reductants and compared their structures, electrochemistry, and reactivity with those of previously reported analogues. The structures show similar features to other related compounds, notably

C–H bond functionalization: recent discoveries and future directions

• Indranil Chatterjee

Beilstein J. Org. Chem. 2023, 19, 1568–1569, doi:10.3762/bjoc.19.114

• feedstocks, the introduction of functionality at specific positions of molecules without requiring any prefunctionalized precursors, and the conversion of light alkanes to higher-value analogues [1][2]. The nonnecessity of prefunctionalization provides a step-economic alternative to classical reactions as

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• ZnMe2 (entries 9 and 10). This difference can be ascribed to a less favorable homolytic substitution reaction of ZnMe2 in relation to its higher analogues and is in line with previous literature observations [11]. The configuration of the major diastereomer was determined by chemical correlation (Scheme

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• explored as catalysts for the hydrosilylation of ketones. Besides the type of the ligand in the NHC–Cu(I) complex, the counter anions (BF4 and PF6) also influenced the catalytic activity. Furthermore, the cationic complexes were found to be more efficient than the neutral analogues under similar conditions

• -naphthol moiety 193 afforded the highest yield and enantioselectivity. On protecting the hydroxy group in the ligand as methyl ether, the reaction efficiency decreased remarkably. However, on using NHC ligands without oxygen atom, such as analogues of 193, IMes, and SIMes, no conversion occurred. 2.8 C(sp2

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• ELs [37], their quantification [38], their biological functions and their role in physio-pathological situations [39][40] invited the researchers to propose new analogues of ether lipids and to study their effects on biological systems. Most of the time the synthetic analogues of ELs aimed to interact

• the scientific community for different reasons: 1) to have an overview on the methods already available, 2) to invite scientists that are working on synthesis methodology to apply their works to the design of ELs analogues, 3) the methods reported in this review can be useful tools for the scientific

• sections also include some examples of non-phosphorus glycosylated antitumor ether lipids (GAEL) but more details on the biology of these ether lipids can be found elsewhere [49][50][51]. The synthesis of analogues of archaeal ether lipids is not included herein but the reader can refer to other articles

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[f]chromeno[2,3-h]quinoxalinoporphyrins

• Chandra Sekhar Tekuri,
• Pargat Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2023, 19, 1216–1224, doi:10.3762/bjoc.19.89

• paramagnetic nature of copper(II) ions [44]. Conclusion In summary, we have successfully synthesized a new series of copper(II) benzo[f]chromeno[2,3-h]quinoxalinoporphyrin analogues in good yields following the one-pot synthetic strategy applying the reaction of copper(II) 2,3-diamino-meso-tetraarylporphyrins

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• highlights photo- and electrochemical methods for recycling amines and NADH analogues that can be used as electron donors in artificial photosynthesis. Important properties of sacrificial donors and recycling strategies are also discussed. Compounds from other fields, such as redox flow batteries and

• NADH-analogues are the subject of most studies for recycling sacrificial donors. NADH has been electrochemically recycled but a careful control of pH is required to prevent dimerization reactions [44][45]. For example, Glusac and co-workers recycled BIH and acridine analogues using platinum electrodes

• in acetonitrile with proton donors [45]. They carefully calculated the pKaH of their proton donors and NADH analogues to control the PCET and to prevent side reactions. In another interesting example, NADH was recycled at a copper electrode in aqueous buffers and NADH was found to be more stable in a

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• effects of compound 1 and related analogues could be realized by C-3 hydrolysis. In 2010, Liu et al. also demonstrated the major role played by changes at C-16 on antibacterial effects of F. pinicola steroids [33]. The acetylation at C-16 reduced the potency compared to the corresponding congener with a

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

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

• -naphthofuran or benzofuran analogues. The achiral phosphoric acid (PhO)2P(O)OH was the catalytic reagent to execute the process delivering the products with low to moderate chemical yields. Attempts to make the process stereoselective, a series of chiral phosphoric acid catalysts were screened in the model

• substituent at the aforesaid position for which a much diminished enantioselectivity (44%) was obtained (Scheme 24) [54]. Pyrophosphoric acids In 2018, Ishihara and co-workers demonstrated a highly para-selective aza-Friedel–Crafts process using phenols and ortho-monosubstituted phenol analogues 104. As

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

• shown that for the hydroxy derivatives the main pathway of phototransformation is a 6π-electrocyclization of the 1,3,5-hexatriene system and subsequent [1,9]-H sigmatropic shift leading to dihydrobenzo[h]pyrano[2,3-f]quinazolines. At the same time, for methylated analogues the photoreaction proceeds in