Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• of amides from 2-alkynylanilines by using TFBen (benzene-1,3,5-triyl triformate) as a CO source, Pd(OAc)2, DPEPhos (bis[(2-diphenylphosphino)phenyl] ether), and DIPEA (N,N-diisopropylethylamine) in MeCN. After 24 h, Pd(OAc)2 and AlCl3 were added to promote a selective cyclization reaction [14]. The

• selective cyclization to the indole derivative in the presence of Pd(OAc)2 and AlCl3. A variety of indole derivatives were synthetized in good isolated yields (Scheme 3). Synthesis of indoles by Pd(II)-catalyzed carbonylation reaction Oxidative carbonylation reactions, as well as all other types of

• targeted products were isolated in good yields (Scheme 5). In 2014, Shen and co-workers developed a selective synthesis for methyl 1-benzyl-1H-indole-3-carboxylates and bis(1-benzyl-1H-indol-3-yl)methanones [18] starting from the same kind of substrates used by Gabriele’s group two years before. The first

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

• , indicating that CoTPS5 is highly selective for individual prenyl substrates and that the reaction is tightly regulated under different conditions. Notably, CoTPS5 was the first plant TS to produce 10 [22]. Although many MSTSs exhibit a broad substrate scope in vitro, their product profiles may be altered in

• selective sesqui-TSs failed to transform 104–112. After further modification with cytochrome P450 CYP720B1 in the yeast host, 28 noncanonical terpenoids were generated, 10 of them are shown in Figure 8c (113–122) [58]. Notably, the widespread biosynthesis of C16 terpenoids was reported in a recent study in

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

• followed by a sequential Jones oxidation. The overall method displays a broad scope and good enantioselectivity, favoring the (R) enantiomer. The applicability of the protocol is highlighted by the efficient enantioselective syntheses of the selective phosphodiesterase-4-inhibitor rolipram and the

• Heck adducts (methyl N,O-acetals) were efficiently converted into several arylated γ-lactams by a simple oxidation procedure (Jones oxidation). To demonstrate the applicability of the strategy, two of the chiral aryl-lactams were further derivatized to provide the selective phosphodiesterase-4

• ). Synthesis of (R)-baclofen hydrochloride (6) from 4dd and (R)-rolipram (5b) from 4de To further demonstrate the applicability of this method, the aryl-lactams 4dd and 4de were successfully converted into the selective phosphodiesterase-4 inhibitor (R)-rolipram (5b) [15], and the commercial drug (R)-baclofen

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• fluorides were also observed as by-products. Given the increasing interest in acyl fluorides in organic synthesis and the attractive features of BT-SRF salts as reagents for organofluorine chemistry, we considered whether optimisation of the reaction conditions could allow for the selective synthesis of

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• ][42][43][44][45][46][47]. The remaining known methods use only both positions to induce cyclization [25][31][32][33][48][49][50][51][52][53][54][55][56]. Therefore, to the best of our knowledge, there are no known methods that allow the selective reaction of both positions of uracil (Figure 2). In

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

• natural products and pharmaceutical agents, including antifungal drugs [1][2][3], and hence their selective preparation has attracted considerable attention from the synthetic community. Compared to methods for the de novo construction of azole heterocycles, direct functionalization of the azole N–H bond

(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

• , deiodination at the bridgehead position, and nucleophilic substitution at the alkyl chloride. From 1,2-BCP (±)-4, a variety of 1,2-BCPs were prepared through basic chemical transformations (Scheme 1B) [26]. Selective deprotection gave access to free alcohol-containing 1,2-BCPs (±)-5 and (±)-8. Oxidation and

• -workers reported a method for the selective bridge bromination of BCPs, giving access to brominated 1,2-BCP (±)-16 (Scheme 2) [33]. By exploiting the homolytic cleavage of the C–Br bond using in situ-generated silyl radicals, they were then able to harness the installed bromide functionality in

• development of a new synthetic route to diester 1,2-cubane 88 from dimethyl cubane-1,4-dicarboxylate (85) (Scheme 9A) [51]. 1,4-Cubane 85 is photochemically carboxylated to 86, and selective saponification of the least hindered ester leads to 87. Formation of a redox active ester followed by photocatalytical

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

• explored the reactivity of ortho-functionalized diaryliodonium salts containing electron-withdrawing groups (EWGs) such as fluorine and nitro groups [29][30]. These ortho-substituted diaryliodonium salts undergo selective benzocyclizations and arylocyclizations with aromatic acids, leading to 3,4

• investigations demonstrated the ability of diaryliodonium salts for selective mono-arylation of 2-naphthols [34]. In this context, we embark on a strategy to modify the neighbouring position of the diaryliodonium salt with an ester group, presenting a novel copper-catalysed regioselective arylocyclization of

• diaryliodonium salts in a cascade cyclization, the cyclization features a copper-catalyzed activation strategy involving the cleavage of the C–I bond and esterification. The resulting cascade of selective arylation/intramolecular cyclization facilitated the synthesis of 3,4-benzocoumarin derivatives. The

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• nitramine. An enzyme, N-nitroglycine lyase A (NnlA), from the bacterium Variovorax sp. strain JS1663 (Vs NnlA) was recently shown to degrade NNG. This strain was enriched from sludge from the Holston Army Ammunition Plant using selective growth media containing NNG as the only carbon and nitrogen source [20

• were used to inoculate 100 µL of selective growth media (1/5 LB media, 20 µM isopropyl β-ᴅ-thiogalactopyranoside (IPTG), 300 µM 2-NAE or 3 mM NNG, and antibiotic) in a 96-well plate. After overnight incubation at 37 °C, the cells were pelleted by centrifugation and the nitrite quantified by Griess

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• ]octane, while O6 migrated when the C4–OH was axial leading to 2,4-dioxabicyclo[2.2.2]octanes. The formation of both anomers from the non-selective addition of fluoride suggested intermediates with oxocarbenium character. This work has recently been extended by Banwell and co-workers to include a set of

• reduction using NaBH4 as per our previously published approach (Scheme 1) [9]. When α-alkylations are performed using 2, the second alkylation step is faster than the first, meaning that only the dialkylated products are formed [16], and the reduction is highly selective with approach of the reductant from

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• distillation [41]. Under these conditions, exclusive formation of the bis-hydrochlorinated product (not shown) might have been anticipated. Several examples of the hydrochlorination of more complex molecules were reported (Scheme 5). Torii demonstrated the selective formation of chloride 20 when treating enone

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• single pentafluorophenyl ring was prepared through the regioselective nucleophilic aromatic substitution reaction of the p-fluorine atoms in 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin with 9-mercapto-m-carborane. The reaction of this porphyrin with sodium azide led to the selective substitution of

• biomolecules via the nucleophilic aromatic (SNAr) substitution reactions [15][16]. A variety of nucleophiles such as amines [17][18], alcohols [18][19][20], thiols [17][19][21][22][23], and carboranes [17][24][25][26][27] have been studied in selective SNAr substitution reactions of the p-fluorine atoms in

• has become one of the most popular route for the site-selective modification of cysteine residues in bioconjugation technology. We suppose that the maleimide group in porphyrin 11 is a useful target for thiol conjugation via Michael addition reactions [44]. This also concerns biotin-conjugated organic

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• therapeutic drugs [1], agrochemicals [2], veterinary medicines [3], medium supplements for selective microbial/cell culture [4][5][6], food preservatives/colorings [7][8], and biochemical reagents for pharmacological/chemical biology studies [9]. This review has focused particularly on compounds produced by

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• and environmentally friendly adsorbents for the selective adsorption of crocins from an aqueous solution of saffron pollen [25]. Pharmacological activity of crocins Various pharmacological studies have shown that crocins are effective against diseases of the central nervous system (neurodegenerative

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

• depsipeptide ring and broad tolerance for structural variation [84]. To simplify the synthetic process and expedite the comprehensive structure–activity relationship analysis, they modified the preparation of the linear chain elongation intermediate and conjugated the late-stage P450-catalyzed selective

• diverse range of heteroaromatics. For instance, incorporation of a 4-methylpyrazole ring (64a) showed nearly complete conversion to product with no measurable starting substrate or hydrolytic byproducts. After producing these cryptophycin analogs utilizing the CrpTE, the selective epoxidation using wild

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

• , which is present in pharmaceutically active substances. The methodology application is showcased by transforming the obtained 4-azido-6,7-dimethoxy-2-sulfonylquinazolines into the α1-adrenoceptor blockers terazosin and prazosin by further C2-selective SNAr reaction and azide reduction. Keywords

• position of quinazolines requires longer time, higher temperatures, and sometimes the use of expensive transition-metal catalysts [12]. A selective C2 modification can be achieved by using 2-chloroquinazolines IV, where the C4 position is blocked by an unreactive C–C or C–H bond (Scheme 1). Cyclization

• terazosin and prazosin [20]. Herein, we report the use of the sulfonyl group dance to synthesize novel 4-azido-2-sulfonylquinazolines and their C2-selective modification in SNAr reactions. In addition, we offer an approach for the synthesis of terazosin and prazosin, known medications against hypertension

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• alkylpalladium radical with the release of dinitrogen. The radical intermediate selectively adds to the double bond of a 1,3-diene or allene, followed by the allylpalladium radical-polar crossover path and selective allylic substitution with the amine substrate, thereby leading to a single unsaturated γ- or ε

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• experimental and theoretical approaches, we clarified the range of applicable substrates for the thermal [2 + 2] cycloaddition of Li+@C60, highlighting the expanded scope of this straightforward and selective functionalization method. Keywords: electron transfer; fullerene; ion-endohedral fullerene; Lewis

• of this straightforward and selective reaction for Li+@C60. Results and Discussion We began by performing density functional theory (DFT) calculations to screen the substrates with suitable HOMO levels for the thermal [2 + 2] cycloaddition with Li+@C60. The structures of several kinds of possible

• unreacted Li+@C60 serves as an oxidant for the reduced monoadducts potentially generated by SET from reactants to monoadducts. These factors contribute to the suppression of multiadduct formation, resulting in the selective generation of the target monoadducts. Specifically, Li+@C60, influenced by the

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• the ECD data for 1 and its known analogs. Polycavernoside E (1) showed selective antitrypanosomal activity against Trypanosoma brucei rhodesiense with an IC50 value of 9.9 μM. This discovery provides additional evidence that polycavernosides, previously thought to be derived from red algae, are

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• was discovered in the 1950s and is produced by the soil bacterium Streptomyces hygroscopicus [1]. It has broad spectrum antibiotic activity, antitreponemal activity against the pathogen that causes swine dysentery, and selective activity against the spirochete that causes Lyme disease [1][2][3]. It

Possible bi-stable structures of pyrenebutanoic acid-linked protein molecules adsorbed on graphene: theoretical study

• Yasuhiro Oishi,
• Motoharu Kitatani and
• Koichi Kusakabe

Beilstein J. Org. Chem. 2024, 20, 570–577, doi:10.3762/bjoc.20.49

• important. A selective hydration of the polar moiety while keeping the pyrene moiety stable can relatively strengthen the stability of conformation 2. Thus, as the polarity of the solvent increases, the probability of conformation 2 appearance is expected to increase. Mechanism of bi-stability in PASE on

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• ], drospirenone (exhibits high affinity to progesterone receptors and is used as a birth control medication) [26][27], griseofulvin (an antifungal agent used to treat fungal infections of the fingernails and toes) [28], as well as oliceridine (a selective G protein-biased μ-opioid receptor agonist used for

• cyclization step was more selective and the total yield of the desired product was higher. The 6-exo-tet cyclization of intermediate compounds 16 under the action of DBU in acetone at room temperature proceeded within a few minutes, which is much faster than in the case of compounds 14. This can be explained

• attack of the oxygen atom of the ester group on the benzyl bromide residue prevails, with the cleavage of the arylidene succinimide fragment involved in further non-selective processes. The causes of the failed cyclizations in the last two cases can be summarized as follows. The intermediates obtained

Synthesis of photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophene-3(2Н)-ones with a terminal phenanthroline group

• Vladimir P. Rybalkin,
• Sofiya Yu. Zmeeva,
• Lidiya L. Popova,
• Irina V. Dubonosova,
• Olga Yu. Karlutova,
• Oleg P. Demidov,
• Alexander D. Dubonosov and
• Vladimir A. Bren

Beilstein J. Org. Chem. 2024, 20, 552–560, doi:10.3762/bjoc.20.47

• change of the solutions from yellow to dark orange. Subsequent selective interaction with AcO− led to the restoration of the initial absorption and emission properties. Thus, the obtained compounds represent dual-mode “on–off–on” switches of optical and fluorescent properties under sequential exposure to

• series method, compounds 2a–c formed the 2:1 complexes 4a–c with Fe2+ (Scheme 3 and Figure 7). It was found that selective interaction of the resulting in situ complex 4a with AcO− led to restoration of the initial absorption and emission properties [31][32]. Other tetra-n-butylammonium salts (TBAX, X

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

• relationship (SAR) studies on selective inhibitors reduce the prevalence of undesired effects, such as toxicity in mammals [4]. Despite being employed in the field for over three decades, the mode of action of preemergence herbicide cinmethylin (1, Scheme 1) has remained unknown until 2018. At that time, the

• ]pyridines that showed promising inhibition of the plant-specific enzyme FAT, we explored the selective late-stage conversion into the corresponding 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines via different reduction methods. Noteworthy, substituted 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines had remained almost

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

• solution. This concept was further developed with a bis-acridinium cyclophane [31] as a multiresponsive receptor for selective phase transfer. In organic media, this macrocyclic receptor presented an affinity for polyaromatic guests with strong selectivity for perylene. A reversible guest release was

• substrate-dependent allosteric with potential applications for regulating cooperative catalytic reactions. Terpyridine-based tweezers have also been developed by Bencini, Lippolis, and co-workers for the selective recognition of diphosphate with [9]aneN3 unit 17 [48]. When closed with Zn(ClO4)2, the anion

• counter ions, the bis(terpy) complex is exclusively formed in CDCl3/CD3OD 4:1. This complex can be converted to the 1:1 species upon exchange of the triflate with more coordinating chloride anions or directly formed upon closing with ZnCl2. Interestingly, only the closed 1:1 form presents a selective