Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• 73019, United States 10.3762/bjoc.20.92 Abstract Presented here is the design, synthesis, and study of a variety of novel hydrogen-bonding-capable π-conjugated N-heteroacenes, 1,4-dihydropyrazino[2,3-b]quinoxaline-2,3-diones (DPQDs). The DPQDs were accessed from the corresponding weakly hydrogen

• constructed via intermolecular N–H∙∙∙N interactions. However, vacuum-deposited films afforded poor hole transport. In separate work, Bunz et al. reported the serendipitous and understated synthesis of an H-bonding capable 1,4-dihydropyrazino[2,3-b]quinoxaline-2,3-dione (Figure 1a) [23]. In 2018, Takeda et al

• . reported the synthesis, electronic characteristics, and liquid-crystalline properties of several electron-accepting acenes, including 1,4-dihydropyrazinoquinoxalinediones (Figure 1b). The incorporation of strong hydrogen-bonding interactions facilitated the formation of a highly ordered liquid-crystalline

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• viral replication in cell-based antiviral assays [24]. That study highlighted the beneficial role of the tyrosine residue and the indispensable role of the C-2 substitution. In this work, we report the synthesis and biological evaluation of further analogues of HeE1-2Tyr (1) against the SARS-CoV-2 RdRp

• and thiadiazolopyridone derivatives because molecules based on these cores have already shown promising antimicrobial activities [25][26]. Results and Discussion Synthesis of HeE1-2Tyr (1) structural analogues Modification of the core: synthesis of pyridobenzoxazole derivatives The synthesis of the

• the benzoxazole ring-opening reaction, namely 16. Simplification of the hit molecule: synthesis of pyridone derivatives We decided to simplify the relatively large structure of HeE1-2Tyr (1) in order to obtain smaller, more accessible inhibitors with similar or better properties. The employed novel

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• wide range of substituents on (hetero)aryl iodine(III) compounds, including electron-rich, electron-poor, sterically congested, and acid-labile groups, as well as a broad range of aliphatic and aromatic carboxylic acids for the synthesis of diverse aryl(TMP)iodonium(III) carboxylates in high yields

• presence or absence of transition metal catalysts under thermal or photochemical conditions [2][3][4][5]. Furthermore, these compounds have practical applications in the synthesis of radiochemicals utilized in positron emission tomography (PET) imaging [6], as well as serving as photoacid generators for

• -arylation using aryl(2,4,6-trimethoxyphenyl)iodonium(III) acetates [13]. In this process, the acetate ligand acted as a base to activate the phenol group and positioned it in proximity to accomplish the smooth SNAr reaction. The synthesis of diaryliodonium(III) salts with various counterions, such as

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

• the synthesis of high-value compounds. Given the great importance of heterocyclic compounds, the carbonylative approach has become increasingly important for their synthesis. In this mini-review, as a class of benzo-fused nitrogen-containing heterocyclic compounds, we summarized and discussed the

• recent achievements on the synthesis and functionalization of indole derivatives via carbonylative approaches. Keywords: carbonylation; functionalization; indole; metal catalyst; organometallic chemistry; Introduction Indole is a heterocyclic compound consisting of a benzene ring fused with a pyrrole

• ][4]. The indole core is particularly noteworthy for its role in various biologically active compounds and drugs, such as antihypertensives, anti-inflammatories, antimycotics, antimigrants, anticancer drugs, and many others [5][6][7]. The first synthesis of indole has been introduced by Fischer in

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

• new route was developed to access a pool of unnatural terpenoids. It is worth noting that the rational design and synthesis of analogs play a valuable role in elucidating the cyclization mechanism of TSs, which further broadens our knowledge of the biosynthesis of terpenoids. Naturally occurring

• selectivity with the noncanonical prenyl substrates. To enable the biotechnological synthesis of irregular terpenes, the product selectivity of 2-methylenebornane synthase from Pseudomonas fluorescenes was altered using a semi-rational engineering approach [56]. In contrast to GPP methylation, modification of

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

• showcase the versatility of these new tetrazole building blocks by integrating the tetrazole moiety into various multicomponent reactions (MCRs), which are already significantly employed in drug discovery. This technique represents a unique and complementary method to existing tetrazole synthesis processes

• 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

• ]. In stark contrast, a method for the synthesis of drug-like tetrazole compound libraries involving a building block approach have remained elusive, with success being reported thus far only with the tetrazole amine [14][15]. The use of a tetrazole building block in MCRs would have all the advantages

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

• commercial drug baclofen as hydrochloride. Keywords: desymmetrization; enantioselective Heck–Matsuda reaction; lactam synthesis; N,N-ligands; palladium; Introduction Desymmetrization reactions consist in the modification of a molecule with the loss of one or more symmetry elements, such as those which

• preclude chirality as in the transformation of a prochiral molecular entity into a chiral one [1]. It is a powerful and elegant strategy in asymmetric synthesis [2], which combined with the use of chiral ligands and transition-metal catalysts enabled many valuable transformations to increase molecular

• ). 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

• Kingdom 10.3762/bjoc.20.82 Abstract 2-(Trifluoromethylthio)benzothiazolium triflate (BT-SCF3) was used as deoxyfluorinating reagent for the synthesis of versatile acyl fluorides directly from the corresponding carboxylic acids. These acyl fluorides were reacted with amines in a one-pot protocol to form

• . Keywords: acyl fluorides; amides; benzothiazolium salts; carboxylic acids; deoxygenative reactions; Introduction Acyl fluorides are attracting much attention as versatile reagents for different applications in organic synthesis. In addition to their use as sources of fluoride ions, they are most commonly

• afford (trifluoromethyl)thioethers, while subsequent work focused on the direct deoxygenative synthesis of fluorinated thioesters from carboxylic acids [29][30][31]. In each case, the reactions proceeded smoothly under operationally simple conditions while BT-SCF3 and related BT-SRF reagents are easy-to

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• Chemistry and Center for Green Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, USA 10.3762/bjoc.20.81 Abstract A new method for the synthesis of heterocyclic systems containing tetrazole and tetrahydroisoquinoline is developed via the performance of one-pot Ugi-azide

• fused imidazotetrazolodiazepinones (Scheme 2A) [37]. The Gámez-Montaño group introduced a one-pot synthesis of Ugi-azide/N-acylation/Diels–Alder/dehydration reactions for isoindolin-1-one and 1,5-DS-T in a linked manner (Scheme 2B) [41]. The Ding group developed sequential Ugi-azide/Ag-catalyzed

• oxidative cycloisomerization reactions for the synthesis of 2-tetrazolyl-substituted 3-acylpyrroles (Scheme 2C) [42]. The Ding group also reported sequential Ugi-azide/Staudinger/aza-Wittig/addition/Ag-catalyzed cyclization reactions for obtaining 12-tetrazolyl-substituted (E)-5H-quinazolino[3,2-a

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

• Abstract The development of a new and straightforward chemoselective method for the synthesis of uracil-based structures by combining Suzuki–Miyaura and Sonogashira–Hagihara cross-coupling is reported. The methodology was applied to synthesize a series of novel compounds. The tolerance of the combination

• a targeted enzyme [21][22][23]. One of these focus areas was the synthesis of alkyne-linked derivatives. The first alkyne-linked compound was already published in 1976, accompanied by new synthesis methods in the following years [24][25][26][27]. With the discovery of potential antiviral properties

• this work, we report a new chemoselective method for the synthesis of a series of hitherto unknown uracil-based compounds by combining Suzuki–Miyaura and Sonogashira–Hagihara cross-coupling [60][61]. The method is designed to be flexible and could also be used to synthesize other structural motifs

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

• attributed to its much greater Lewis basicity compared to other azoles, likely killing the reactivity of the iodine(III) electrophile by direct coordination. The present reaction could be performed on a preparative scale. Thus, 1 mmol-scale synthesis of the vinylazoles 4aa and 4ba could be successfully

• other heteroatom nucleophiles is currently underway. Synthesis of N-vinylazoles. Scope of three-component N-alkenylation of azoles. Competition experiments and plausible reaction pathway. Preparative-scale reaction and product transformations. Reaction conditions: (a) Pd(PPh3)4, 4-MeOC6H4B(OH)2, Cs2CO3

(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

• straightforward synthesis of a wide-range of disubstituted BCPs from [1.1.1]propellane allows them to be easily integrated into drug discovery programmes. The case of Darapladib is one well-known example of a productive para-benzene-to-BCP bioisosteric switch [24]. By comparison, the number of bioisosteres of

• . Bennet and co-workers also reported the synthesis of 1-amino-1,2-BCPs (±)-11a–e via a similar strategy (Scheme 1C) [29]. They were able to prepare differently-substituted [1.1.1]propellanes 3b–f and subject these to strain-release amination reactions. The synthesis was shown to tolerate typical alcohol

• ) [32]. The synthesis of the corresponding 2-aza-1,5-BCHs 13 was achieved by an intramolecular photochemical [2 + 2] cycloaddition. They were able to employ this synthetic route to synthesise a variety of 1,2-BCPs (±)-14 bearing a protected amine in the bridge position. In early 2023, MacMillan and co

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

• process. Derivatization of spiroviolene for X-ray crystallography. A) Hydroboration/oxidation reaction of spiroviolene involving a borane migration process. B) Synthesis of the hydrazone derivative of spiroviolene for single-crystal X-ray diffraction. Supporting Information Supporting Information File 19

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

• . Keywords: annulation; arylocyclization; 3,4-benzocoumarin; diaryliodonium salts; naphthol; Introduction Diaryliodonium salts as electrophilic reagents have attracted significant attention in the field of organic synthesis owing to their efficiency and selectivity [1][2][3][4][5][6][7]. Particularly, they

• for the synthesis of functional materials via cross-coupling reactions. Next, we extended our investigation to 1-naphthol in this reaction, and found that the arylation of 1-naphthol was achieved selectively at the C-2 position. The cascade cyclization resulted in the corresponding products 3an and

• 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

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

• ) is produced selectively when cellulose-containing materials, including lignocellulosic biomass, are acidified and pyrolysed [1][2]. Lab scale synthesis of this chiral material can be accomplished in a single step without special glassware [3], while large scale production of the reduction product

• the glycosidic bond using an organometallic purine or pyrimidine derivative and an electrophilic furanose derivative [23][25]. This process can result in anomeric mixtures, so 5 has potential applications in targeted synthesis, as the configuration of the pseudo-anomeric centre matches the common

• biological ribosides. This prompted an investigation of the scope of the SOCl2-mediated rearrangement, with the aim of producing useful chiral materials for synthesis. Results and Discussion The set of bicyclic systems 10a–f with a C4 alcohol were prepared starting with cyrene (2) by alkylation and then

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

• identical with the drimenol standard, suggesting successful synthesis of drimenol. This confirms CavC as a DMS, and the cav BGC is likely responsible for the biosynthesis of compounds 2–4. CavA, a P450, responsible for the formation of C-2 and C-3 hydroxy groups It was hypothesized that compound 1 serves as

• 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

• efficient chemoenzymatic synthesis of DMTs or drimanyl indoles [44]. (a) Representative bioactive drimane-type sesquiterpenoids (DMTs). (b) Reported biosynthetic pathways of DMTs from fungi. Chemical structures and HPLC analysis. (a) Chemical structures of isolated sesquiterpenes 2–4 from S. clavuligerus

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• focusing on hydrochlorination reactions. Firstly, an outstanding overview, including extensive research from the former Soviet Union, was reported in 1982 by Sergeev and co-workers [12]. Secondly, the chapter on “Addition of H-X Reagents to Alkenes and Alkynes” in comprehensive organic synthesis gives a

• solution of HCl, even in the presence of secondary alcohol and ester functionalities (Scheme 5B) [45]. An application in the synthesis of Δ9-tetrahydrocannabutol, the butyl homologue of Δ9-tetrahydrocannabinol (Δ9-THC), is outlined in Scheme 5C [46]. In this case, ZnCl2 was employed as a catalyst, but

• reported. In surface-mediated reactions, the proton donor is typically Si–OH or Al–OH. For clarity in discussing subsequent reactions, we have separated the in situ HCl gas synthesis from the hydrochlorination. It is important to note that these reactions are one-pot processes rather than two-pot reactions

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• of hydrophilic oligopeptide anchors (oligo-Lys, oligo-Glu, and oligo-Arg) were synthesized. A previously reported Prato reaction adduct of a biscarboxylic acid-substituted C60 derivative was subjected to a solid phase synthesis for amide formation with N-terminal amines of peptides on resin to

• suitable for the coupling to peptides on resin, prepared by solid-phase peptide synthesis (SPPS) [35]. The detailed conditions for the amide-forming reaction were optimized using biscarboxylic acid-substituted C60 derivative 3 and a similar peptide with a primary amine derived from γ-aminobutyric acid

• (GABA) at the N-terminus of the Lys pentamer peptide on resin. Using the optimal reaction conditions, three types of hydrophilic peptide pentamers on resin, oligo-Lys (2a), oligo-Glu (2b), and oligo-Arg (2c), were subjected to the reaction with 3 for the synthesis of C60–peptide conjugates 5a–c (Figure

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

• synthesis and characterization of tris(carboranyl)porphyrins of A3B-type (where “B” corresponds to the substituent responsible for bioconjugate coupling) based on the transformations of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin which was used as a basic compound for the synthesis of new boronated

• conjugates with functionalized linker groups suitable for bioconjugation or which may be efficient for PDT and BNCT improvement. Results and Discussion Synthesis Nucleophilic substitution reactions of the four p-fluorine atoms in 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (1) are well studied [15][16

• and the data are given in Table 1. The 11B NMR signals of compounds 5–7, 11, 12, 14, 18–20, 23, 24, and 26 are in the range from δ = −0.9 to −17.0 ppm confirming the closo-structure of the carborane polyhedra. Conclusion In this article a synthesis of A3B-type carboranylporphyrins as potential

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

• the tetR regulator have been reported in several studies as methods to improve target-substance production capacity. Interestingly, Wilbanks et al. reported the structure–activity relationships of bacterial hormones in secondary metabolite biosynthesis by diversifiable synthesis [41]. The ability to

• ribosomal S12 protein mutation results in increased expression of translation factors, which leads to enhanced protein synthesis in secondary metabolism [47]. Liu et al. reported activation of the production of bohemamines 11–13, bacterial alkaloids containing a pyrrolizidine core with two unusual methyl

• higher yield of validamycin A (25) from Streptomyces hygroscopicus 5008 together with more rapid protein synthesis and sugar consumption by subjecting cultures to one or more NaOH shocks [66]. Ren et al. obtained enhanced ε-poly-ʟ-lysine (ε-PL, 26) production by acidic pH shock of Streptomyces sp. M-Z18

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

• -inflammatory properties, hepatorenal protection, and anticancer activity. They are often used as coloring and seasoning agents. Due to the limited content of crocins in plants and the high cost of chemical synthesis, the supply of crocins is insufficient to meet current demand. The biosynthetic pathways for

• cell suspension culture, heterologous biosynthesis, and total synthesis [16][17]. Crocins can be obtained from plant cell culture, but the production is prone to epigenetic silencing and toxic intermediates. The chemical synthesis of crocins is challenging due to the presence of numerous chiral centers

• -synuclein (αS), thereby alleviating the apoptosis of neuronal cells and cognitive impairment [30][31][32][33]. Lastly, the extract of C. sativus can also improve the chronic stress-induced loss of learning and memory by reducing the ROS level or regulating the synthesis of superoxide dismutase (SOD) and

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• conjunction with 13C NMR to investigate substrate acceptance by BaeJ-KS2 from module 4 of the bacillaene PKS. Results and Discussion Synthesis of N-acetylcysteamine thioesters Previous studies have shown that N-acetylcysteamine thioesters (SNAC esters) can be uploaded to KS domains [22][23][24][25]. Therefore

• , to investigate the function of the KS domain BaeJ-KS2 the synthesis of 13C-labelled (S)-11 as a mimic of the intermediate bound to the ACP of module 3 was performed. It was planned to introduce the 13C-labelling from (5-13C)glutamate into the γ-aminobutyrate portion of (S)-11. For this purpose, the

• = thioesterase. The black dot indicates a methyl branch introduced by the β-branching cassette. Synthesis of the BaeJ-KS2 substrate surrogates (S)-11 and (R)-11. Green dots represent 13C-labelled carbons. Supporting Information Supporting Information File 76: Experimental part and NMR spectra. Acknowledgements

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

• .20.66 Abstract Chemoenzymatic strategies that combine synthetic and enzymatic transformations offer efficient approaches to yield target molecules, which have been increasingly employed in the synthesis of bioactive natural products. In the biosynthesis of macrocyclic nonribosomal peptides, polyketides

• , and their hybrids, thioesterase (TE) domains play a significant role in late-stage macrocyclization. These domains can accept mimics of native substrates in vitro and exhibit potential for use in total synthesis. This review summarizes the recent advances of TE domains in the chemoenzymatic synthesis

• for these natural products that aim to address the common issues in classical synthetic approaches and increase synthetic efficiencies, which have the potential to facilitate further pharmaceutical research. Keywords: biosynthesis; chemoenzymatic synthesis; macrocyclic peptides; macrocyclic

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

• Julien Borrel Jerome Waser Laboratory of Catalysis and Organic Synthesis, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL SB ISIC LCSO, BCH 4306, 1015 Lausanne, Switzerland 10.3762/bjoc.20.64 Abstract We report the detailed background for the

• discovery and development of the synthesis of homopropargylic azides by the azido-alkynylation of alkenes. Initially, a strategy involving SOMOphilic alkynes was adopted, but only resulted in a 29% yield of the desired product. By switching to a radical-polar crossover approach and after optimization, a

• terminal azide, despite its implication in the synthesis of complex molecules [3][6]. Therefore, the development of a straightforward reaction to synthesize homopropargylic azides would be of general interest. The azido-alkynylation of alkenes would allow to generate the desired motif in a single step

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• enhanced economic efficiency, eco-friendly practices, and reduced waste. Catalysts with the highest enantioselectivity have been employed in the synthesis of essential chiral intermediates for drug production, such as amprenavir [12], rivaroxaban [13][14], linezolid [13] and salmeterol [7]. Therefore

• . Acknowledgements The parts of this work were published in the diploma thesis by Karel Chlumský (“Synthesis and catalytic application of chiral 2,2'-(pyridine-2,6-diyl)-bis(imidazolidine-4-ones”) and in the diploma thesis by Jan Mrkvička (“Synthesis and catalytic application of 2-(proline-2-yl)imidazole”).