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

• enzymes in crocin biosynthetic pathways CCDs: Crocin biosynthesis initiates with the catalytic cleavage of the C‒C double bond by CCDs at various sites of the carotenoid skeleton. The cleavage generates a carbonyl group at the end of the formed carotenoid derivatives [88]. The CCD family can be

• CsCCD2 that exhibits broader substrate specificity and higher catalytic efficiency through computational modeling. Heterologous expression of the S323A mutant of CsCCD2 in yeast led to a 4-fold enhancement in the production of 1, with a crocetin (1) titer of 107 mg/L in a 5-liter fed-batch fermentation

• supply, overexpressing PsBCH-CsCCD2, and optimizing the fermentation medium, the yield of crocetin (1) reached 12.43 ± 0.62 mg/L in a 5 L bioreactor [115]. While CCD has a higher catalytic activity at low temperature, the biosynthesis of zeaxanthin (7) is more suited to a higher temperature. As such, Liu

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

• only for the incorporation of one extender unit [2][3]. Although enzyme domains with various specialised catalytic functions can be found as integral part of polyketide synthases, three domain types are fundamental to their biosynthesis, resembling the same logic as observed for fatty acid biosynthesis

• ester 5 was coupled with the carboxylic acid (S)-8, derived from ʟ-leucine ((S)-6) via hydroxyacid (S)-7, to yield the amide (S)-9. Deprotection through catalytic hydrogenation to (S)-10, saponification of the acetate ester and Steglich esterification with N-acetylcysteamine gave access to the desired

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• AsCPS synthesized copalyl diphosphate and that AsPS then converted it to (−)-sandaracopimaradiene. Since AsPS and AsCPS have distinct domain organizations from those of known fungal TCs and are likely generated through fusion or loss of catalytic domains, our findings provide insight into the evolution

• gene (AsGGS), suggesting that they are related to the biosynthesis of diterpenes (Figure 2A). AsPS and AsCPS consist of αβ and αβγ domains, respectively. Further sequence analysis revealed that the β domain of AsPS contains a mutation at the catalytic aspartic acid residue, indicating that this enzyme

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

• since it is known to be reduced by photocatalysts such as Cu(dap)2Cl [17]. This perfectly fits a catalytic cycle involving the reduction of Ts-ABZ (3) followed by oxidation of the carbon radical to form a carbocation and regenerate the ground state catalyst. Styrene (1a) was used as model substrate

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

• based on derivatives of imidazolidin-4-one were synthesised and characterised. The catalytic activity and enantioselectivity of their corresponding copper(II) complexes were studied in asymmetric Henry reactions. It was found that the enantioselectivity of these catalysts is overall very high and

• itself constitutes a stereocentre [4]. The specific pairing of a chiral ligand and a metal ion is essential for the catalytic characteristics and its effectiveness of the complex in asymmetric syntheses [1][2][3]. In recent years, our research group has synthesised a series of chiral ligands based on 2

• catalytic arrangements of the most enantioselective catalysts, including anchoring on polystyrene beads [8][9], magnetic nanoparticles [10], or block copolymers composed of PEG-poly(Glu) [11]. These modifications have facilitated the recycling of the catalysts, offering numerous advantages, including

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

• (PPh3)2Cl as catalyst, the model reaction also afforded the corresponding product 4a in 31% yield, demonstrating the H–Pd(II)–X species could be a possible catalytic species (Scheme 4d). According to the UV–visible spectra, the only absorbing species at 467 nm consists in the pre-catalytic system Pd(OAc

• subsequent attack of amine 3 at the latter stage would afford the unsaturated ε-AA derivative 4 and regenerates the Pd(0)Ln to close the catalytic cycle. Different from the reactive site of 1,3-diene, the hybrid alkylPd radical I selectively adds to the central position of the allenyl group of allene 5a

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• sphere, accessing more diverse fused imidazolium frameworks and different peripheral functionality offers significant scope to influence catalytic properties. Few studies into L-shaped imidazolylidines have explored core motifs beyond ImPy, with NHCs derived from two π-rich rings fused together

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

• is relatively high. However, this is similar to other myo-inositol dehydrogenases whose KM values are also in the mM range [12][16]. Hyg17 showed a higher catalytic efficiency of 366.7 ± 46.96 M−1 s−1 with myo-inositol as compared to the 29.6 ± 5.28 M−1 s−1 for scyllo-inositol. This reduced catalytic

• efficiency can be attributed to the reduced kcat and increased KM for scyllo-inositol over myo-inositol. We also found that the catalytic efficiency for NAD+ was 452.4 ± 54.49 M−1 s−1 (Table 1 and Figure 2f). Sequence similarity network We generated a sequence similarity network (SSN) for the protein family

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• analyses of these enzymes and the invention of AlphaFold2 have facilitated access to their structures. Structure-based mutagenesis combined with applications of unnatural substrates has further diversified the catalytic repertoire of these enzymes. The information in this review provides useful knowledge

• residues, the catalytic activities of these enzymes were exchanged [34]. From 24, PrhA V150L/A232S produced 27, and AusE L150V/S232A produced 28. Surprisingly, PrhA V150L/A232S/M241V catalyzed additional oxidations of 27 to produce compounds 29 and 30, as unnatural products. As demonstrated in these

• compounds (40, 43, 44, 47, 48, 50, 51, and 53–55) (Figure 7A). In addition, a structure-based mutagenesis study of SptF was performed to further amplify its catalytic potential. Firstly, the hydrophobic residues Ile63, Phe133, and Ile231, which compose the substrate binding site of SptF, were mutated. As a

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

• in acetonitrile. However, the simplest and most effective method was the addition of a catalytic amount of HClO4 [14]. Although studies on photoacylotropic systems have been carried out for some time [14][16], only within the framework of this work, a method for the preparative synthesis of

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

• quinolines and indoles [24], pyridines [25], and imines [26], the reactions of 5 and 15c with ammonia borane (3 equiv) in the presence of a catalytic amount of B(C6F5)3 in toluene as an aprotic solvent at a temperature of 80 °C afforded aminoboranes 17b (R1 = F) and 17c (R1 = CH3) as main products along with

• accordance with the results obtained for dimethylated [1,3]thiazolo[4,5-b]pyridine 15c, the corresponding aminoboranes 17d and 17e were formed when 6-bromo[1,3]thiazolo[4,5-b]pyridine 12c was treated with ammonia borane in toluene at 45 °C in the presence of a catalytic amount of B(C6F5)3 (Scheme 3). Whilst

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

• : (i) metal coordination for closing/opening of the tweezers, (ii) reversible oxidation, (iii) pyrazine guest binding in the oxidized state. Such an example demonstrates the potential of the molecular tweezers architecture to go beyond simple two-level switches and access multilevel systems. Catalytic

• tweezers 16 were then synthetized by Vives and co-workers using a 6,6”-substituted terpyridine this time bearing zinc(II)–salphen complexes [47]. The catalytic activity was evaluated in an acetyl transfer reaction between pyridinemethanol derivatives and anhydrides. For the ortho derivative, a rate

• 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

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• protodeauration was not confirmed [27]. Follow-up studies in our lab revealed that the alkylgold intermediate (2a, Scheme 1) reacts significantly slower than observed rates for catalytic hydroamination, suggesting it is not a viable intermediate in the catalytic cycle [28]. It has been shown that C(sp2)-vinylgold

• were shown to proceed with anti-selectivity and that was used as support for gold catalysis [15], but mechanism studies of triflic acid catalysis showed a preference for anti-selectivity as well [31]. Despite similarities, control studies indicate meaningful differences in catalytic activity between

• generally acidic conditions that initiate cyclization [34][35]. These observations are critical for informing future discussion and experiments related to this important reaction. Results Ligand effect To examine the catalytic activity of gold with ligands of different electronic properties, we used our

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• modular synthases [5]. They used the inhibitors of individual domains to investigate the biosynthetic pathway of blue pigment synthetase A, which produces the blue pigment indigoidine, and demonstrated that their results complement the proposed biosynthetic pathway. Furthermore, among the catalytic domain

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• (Table 1, entries 14–16). The decisive influence of the base for this reaction is probably due to a concerted metalation–deprotonation mechanism [27][28][29][30]. Then, the scope of the Pd-catalyzed direct arylation for access to fluoranthenes was investigated (Scheme 2). The first step of the catalytic

• -aryl-8-bromonaphthalene A (Scheme 2). This catalytic cycle is followed by a second involving oxidative addition of 1-aryl-8-bromonaphthalene A, followed by intramolecular C–H coupling of the two aryl rings to give the fluoranthene derivative. Consequently, the use of arenes bearing substituents at the

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• counterparts, due to their recyclability, ease of handling, and low cost [40]. Carbon-based solid acid catalysts especially are an interesting catalyst class, because they display low corrosiveness, toxicity, and higher catalytic activity, while also being insoluble in most organic solvents. The large amount

• of strong acidic sites that are on the carbon-based solid acids enhance their catalytic ability, compared to traditional Lewis and protic acids [41][42][43]. The most common examples in literature for the reaction of the synthesis of BIMs under solvent-free conditions utilize either protic acids

• . Finally, another nucleophilic attack by a second molecule of indole to IV is occurring, forming the desired BIM 12, while simultaneously releasing the catalyst, rendering it available for another catalytic cycle [80]. Halogen bonding processes Recently, halogen bonding (XB) interactions have emerged as an

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• (3.15 to 2.06 × 105 s−1) [34] when employing catalytic IrIII excited state reductants with moderate reducing potentials (E1/2red[IrIV/*IrIII] ≈ −1.13 V vs Fc0/Fc+ in MeCN) [35]. This suggests that in the absence of a sufficiently strong driving force, BET and fragmentation compete to influence the

• resulting concentration of radicals. In such instances, opting for a stronger catalytic reductant or utilizing a stoichiometric electron donor can greatly improve the efficiency of radical generation. On the other hand, additional factors such as the ability of Brønsted and Lewis acid additives to promote

• hydrogen atom transfer (HAT) or sequential electron transfer and proton transfer (ET/PT) steps. Alternatively, redox-neutral transformations can be envisioned using catalytic reductants, which can enable a complementary scope of downstream functionalizations (Scheme 2B). In this perspective, we present an

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• condensation and Schiff base formation, which is then cyclized [12][16]. The reaction of 1 with arylamines 2a is performed in toluene solution in the presence of a catalytic amount of p-toluenesulfonic acid. This readily affords 6,8-di-tert-butyl-N-aryl-3H-phenoxazin-3-imines 3 but proceeds smoothly only with

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains

• Sharmila Neupane,
• Marcelo Rodrigues de Amorim and
• Elizabeth Skellam

Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32

• of several catalytic domains organized into modules. Typically, a module possesses an adenylation (A) domain for selecting and activating amino- or keto acids, a thiolation (T) domain for shuttling intermediates between catalytic domains, and a condensation (C) domain that catalyzes amide or ester

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• one of the three potential binding sites. In contrast to other R-type lectins such as ricin, it lacks a catalytic domain. As R-type lectins are both a well-investigated family of lectins and widely used in research and beyond, we first wanted to analyze where CMA1 would be situated in the broader

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• to be able to produce meaningful changes in the reactivity of the cage [28][29][30][31][32]. In 2018, our group reported a catalytic process to transform C60 in bis(fulleroid) derivatives [33][34][35]. This transformation encompassed a partially intermolecular Rh-catalyzed [2 + 2 + 2] cycloaddition

• were run using other solvents such as toluene and chlorobenzene, increasing the C70 concentration from 1.2 M to 2.4 M, and decreasing the catalytic load to 5 mol % (Table S1 in Supporting Information File 1). However, none of these trials improved the yield of bis(fulleroid) 2a. The same reaction was

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

• simple compounds. In particular, catalytic domino reactions and one-pot processes with excellent selectivity and functional-group tolerance are of significant interest to industrial and academic research. In the so-called domino reactions, all of the required reagents, the catalyst, and a solvent are

• steps, which is superior to conventional organic synthesis. The Thematic Issue “Catalytic multi-step domino and one-pot reactions” in the Beilstein Journal of Organic Chemistry, which I had the pleasure to edit, covers the recent strategies of domino reactions and one-pot syntheses and presents the

• nucleophilic substitution of benzylic bromides with sodium azide and a subsequent copper(I)-catalyzed double click reaction in one pot [17]. In summary, these contributions by renowned experts demonstrate the broad diversity of impressive catalytic domino, tandem, and one-pot processes towards many valuable

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• crystalline form [55]. It was found that the aliphatic substituents (diacetyl- and distearoyl-) supported faster relaxation rates than the aryl-containing substituents (dibenzoyl- and bis(3,5-dinitrobenzoyl)-). Moreover, addition of catalytic amounts of amines accelerated the backward Z–E isomerization of Z

• working for Battelle Development Corporation, published a patent “Catalytic extraction of stored solar energy from photochemicals”, where the Ν,Ν'-diacylindigo derivatives were utilized as an energy storage element [78]. The mechanism of the energy storage relied upon the photoinduced E–Z isomerization of

• the indigo derivatives (energy accumulation) and the follow-up catalytic or heat-triggered Z–E reaction (energy release). Another example of a patent is “Sunlight-energy-storing substances and sunlight-energy-storing method using the same”, published in 1983 by Matsushita Electric Industrial

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• catalytic cycle. Finally, the acetimidic anhydride D undergoes a Mumm rearrangement to furnish the desired β-trifluoromethyl diacylamino ester 4a. The final goal of this work is the examination of the scale-up applicability of this three-component tandem reaction (Scheme 5). To our delight, the reaction

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• either 1,2-dibromobenzene or 2-bromophenylboronic acid. The 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepinone could be synthezised in good yield using a sequential catalytic procedure, using both C–L and B–H approaches. Gratifingly, the use of the C–L reaction was more impressive, and afforded the

• carried out with Cu. The aminocarbonylation reaction which was introduced by Schoenberg and Heck in 1974 is an efficient catalytic route to carboxamides [11]. It was a major step forward and has been amply applied in a number of carbonylation reactions over the years [12]. In 2011, Buchwald and

• via a cross-coupling reaction with NH3 [13]. The reaction was undertaken in the presence of a catalytic amount of a palladium catalyst and afforded a library of dibenzodiazepinones in good to excellent yields (Scheme 1a). In 2013, Zhang et al. developed a synthetic route leading to structurally