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

• , 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

• polyketides; thioesterase; Introduction Nonribosomal peptides, polyketides, and their hybrids exhibit significant diversity and a broad spectrum of bioactivities [1][2][3]. Particularly, macrocycles from these three categories of natural products are vital resources for developing pharmaceuticals and drug

• possible and provides a potential to construct the analogs library of these bioactive macrocycles for further biological investigations. This review presents representative examples of chemoenzymatic approaches for macrocyclic peptides, polyketides, and their hybrids employing TE domains, and particular

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

• 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

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• version of antiSMASH 7.0 [25] software for the analysis of the Penicillium shentong XL-F41 genome, we identified 46 BGCs. These include 13 NRPS-like fragments, 6 NRPS, 13 type I PKS, 2 PKS/NRPS hybrids, 1 NI-siderophore, 2 NRP-metallophore/NRPS hybrids, 1 fungal RiPP with POP or UstH peptidase types, 1

• fungal-RiPP-like/T1PKS, 1 betalactone, 1 PKS type I/NRPS/indole hybrid, 1 fungal-RiPP-like/T1PKS hybrid, 1 NRP-metallophore/NRPS hybrid, NRPS-like/terpene/phosphonate hybrids, 3 terpenes, and 1 indole-related cluster (Table 5). BGC 7.3, identified as an indole-type gene cluster, includes genes for

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• of hybrids of 1,2,3-triazole with other heterocycles and to identify biologically active compounds among the synthesized compounds. It is known that the cycloaddition reaction of azidopyrimidinediones with enamines [13] represents an effective method for the synthesis of pyrimidinyl amidines [14

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• Maksym Matviyishyn Bartosz Szyszko Faculty of Chemistry, University of Wrocław, 14 F. Joliot-Curie St., 50-383 Wrocław, Poland 10.3762/bjoc.19.120 Abstract Porphyrins and crown ether hybrids have emerged as a promising class of molecules composed of elements of a tetrapyrrole macrocycle and an

• metals. In this perspective article, the overview of both the early designs of porphyrin-crown ether hybrids, as well as the most recent advances in the synthesis and characterisation of this remarkable group of macrocyclic systems, are addressed. The discussion covers the strategies employed in

• synthesising these systems, including cyclisation reactions, self-assembly, and their remarkable reactivity. The potential applications of porphyrin-crown ether hybrids are also highlighted. Moreover, the discussion identifies the challenges associated with synthesising and characterising hybrids, outlining

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

• of the alkene provides the seven-membered cyclic intermediate 203. Subsequent reductive elimination furnishes the endo-annulated product 194 (Scheme 37b). Out of various pyridine-fused heterocyclic hybrids, azaindolines are important scaffolds in natural products and pharmaceuticals serving different

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

• structures developed recently, and, significantly, quinoline-3-sulfonamides are frequently encountered among such pharmacologically active hybrids (Figure 1b) [31][32][33][34]. Despite these facts, the diversity of quinoline-3-sulfonamides reported in the literature is limited due to obstacles in the

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

• the MCR repertoire. Therefore, an urgent problem is to synthesize structurally complex compounds, molecular hybrids containing pharmacophoric and peptidomimetic fragments, to explore their biological activity. The possibility of inserting an unsubstituted imidazo[1,2-a]pyridine fragment into the

• 7a–t in 28–72% yield (Scheme 4, Table 1). Having obtained several new compounds containing substituted imidazo[1,2-a]pyridine and peptidomimetic fragments linked by a CH2O linker, we further explored the possibility of synthesizing similar hybrids without a CH2O linker between the two moieties. The

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• of the synthesis and properties of various porphyrin-triazole hybrids, this review will discuss some of the key reactions involved in the preparation of triazole-linked porphyrin conjugates. Keywords: azide–alkyne; click chemistry; CuAAC; 1,3-dipolar cycloaddition; porphyrin; 1,2,3-triazole

• medicinal chemistry. Owing to the strong absorption in the visible region, these 18π-electron systems also demonstrate excellent photoluminescence properties. Therefore, porphyrin hybrids have been widely used as efficient sensitizers for PDT applications and dye-sensitized solar cells (DSSCs). Because the

• majority of porphyrin hybrids are synthesized by modifying β- and meso-positions of porphyrin, thus numerous chromophoric groups and biologically important scaffolds have been attached to porphyrins at these positions in recent years. In the past, many synthetic procedures have been utilized to covalently

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• ). Moreover, since these assembly line-like pathways follow the same biosynthetic principle, they often form hybrids with other biosynthetic assembly line-like pathways [21]. Prominent examples of the usage of pHMMs are the original algorithm of the antibiotics & Secondary Metabolite Analysis Shell (antiSMASH

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• pharmacological data already available for this class of inhibitors such as compounds 63–65 [115][315]. Indeed, out of the structure–activity relationship of the many series of inhibitors of the ATP-ase function of type IIA topoisomerases discovered, it seems plausible to design and synthesize hybrids, combining

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• family and is associated with a broad spectrum of biological properties. 3-Formyl-9H-pyrido[3,4-b]indole is a such potent precursor belonging to this family which can be tailored for installing diversity at various positions of β-carboline to generate unique molecular hybrids of biological importance

• group has also investigated the scope of 1-formyl-β-carbolines for generating unique molecular hybrids by application of the Morita–Baylis–Hillman reaction [48][49][50]. It was also revealed from a detailed literature survey that only limited reports have been documented toward exploration of 3-formyl

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• observed for cellulose [67][79], while the multifluorinated compound formed considerably shorter platelets. Cellulose–xylan [80] and cellulose–chitin [81] hybrids were also obtained upon enzymatic polymerization of the respective dimers. An amino or azido functionality in the C-6 position allows for

• amylose with narrow MW distribution, amylose hybrids, and amylose-functionalized materials [186]. Linear and branched oligosaccharides with mixed α(1–3) and α(1–4) linkages were synthesized using a glucansucrase from Lactobacillus reuteri [187][188]. Even though several chemical methods are available for

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• multicomponent reaction (IMCR) [31]. The enantioenriched hemiacetals 5 were obtained using the Jørgensen catalyst 7 as previously described by Rueping et al. [32]. This approach enables the rapid assembly of complex natural product hybrids 6 including up to four different molecular fragments, such as

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• double-headed nucleosides 4a,b were dimethoxytritylated (DMTr), phosphitylated, and incorporated into DNA oligonucleotides using the standard automated phosphoramidite method. The UV-based melting temperature (Tm) of hybrids of the modified oligonucleotides with complementary DNA strands were studied

• nucleoside 37 (Scheme 9) [34]. The double-headed nucleoside 37 was dimethoxytritylated, phosphitylated, and incorporated into 11- to 13-mer oligonucleotides using the standard automated phosphoramidite method. The UV-based melting temperature (Tm) of hybrids of the modified oligonucleotides with

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• (GraphPad Software, CA). Components of the LNPs. A) Lipid species and lipidated cell-penetrating peptides applied by postinsertion. B) Graphical representation of aptamer–probe hybrids. LNPs with T7 pass through the transwell cell barrier and are taken up by target cells. HeLa (CCR5-negative control cell

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• fullerene array 213. The synthetic route to conjugates 214 of fullerene with benzothiadiazole. The synthetic route to conjugates 215 of fullerene with diketopyrrolopyrrole. The synthetic route to fullerene–acetylene hybrids. [60]PCBM derivatives containing various aromatic and alkyl groups bound to the C60

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• ]. Fabclavines are hexapeptide/polyketide hybrids derived from nonribosomal peptide synthetases (NRPS) and a polyketide synthase (PKS), which are connected to an unusual polyamine derived from polyunsaturated fatty acid (PUFA) synthases [20]. Beside full-length fabclavines, also shortened derivatives were

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• dried. It was demonstrated that the CuO nanoparticles–graphene hybrids could act as an effective catalyst for the “click” reaction in aqueous medium under aerobic conditions. The reusability of the catalyst CuO–GO was screened as well: the catalyst was recycled by simple filtration and washing with

Synthesis of triphenylene-fused phosphole oxides via C–H functionalizations

• Md. Shafiqur Rahman and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2020, 16, 524–529, doi:10.3762/bjoc.16.48

• nature as hybrids of triphenylene and benzo[b]phosphole. Keywords: C–H functionalization; fluorescence; phosphole; polycyclic aromatic hydrocarbons; triphenylene; Introduction The phosphorus-containing five-membered ring, phosphole, has attracted significant attention as a structural motif in π

• structurally related benzo[b]phosphole and triphenylene derivatives. The optical data illustrate the nature of compounds 8a–c as hybrids of triphenylene and benzo[b]phosphole oxide. Regarding the absorption, 8a and 8b displayed multiple absorption bands from 250–400 nm (Table 1, entries 1 and 2), which

• strong blue fluorescence in solution. The absorption and emission profiles of the π-extended phosphole oxide revealed their characteristics as hybrids of 2,3-dialkoxytriphenylene and 1-phenyl-2,3-dialkylbenzo[b]phosphole. We anticipate that the key intermediate of the present synthesis, 3, and related

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• rhodium(III)-catalyzed intermolecular annulation has been established for the preparation of tetrazole-isoquinolone/pyridone hybrids. Several N-acylaminomethyltetrazoles were reacted with arylacetylenes to form the hybrid products in moderate to very good yields. The method relies on the capacity of the

• /pyridone hybrids by means of a reaction sequence comprising an Ugi-azide-4CR and a Rh(III)-catalyzed annulation as key steps (Scheme 1D). Results and Discussion In previous works, our group has described a variety of synthetic approaches that combine the diversity-generating character of multicomponent

• , compounds 1a–o were reacted with diphenylacetylene under the optimized catalytic conditions to furnish – eventually – the corresponding tetrazole/isoquinolone hybrids 4a–o. We first fixed the R2 substituent as H (derived from paraformaldehyde as aldehyde component in the Ugi-azide-4CR, Scheme 1) to better

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• -4CR, which is indeed one of the MCRs of major incidence in the field of steroid chemistry. Rivera and co-workers were the first to employ this 4CR for the conjugation of amino acids to steroids [19] as part of a general program for the synthesis of peptidomimetic–steroid hybrids [20][21]. As shown in

• -diketopiperazines based on a diastereoselective Ugi-4CR with an androstanic aldehyde derived from dehydroepiandrosterone (DHEA) [16]. Multicomponent synthesis of a heterocycle–steroid hybrid using a ketosteroid as carbonyl component [18]. Synthesis of peptidomimetic–steroid hybrids using the Ugi-4CR with

• with an alkynyl seco-cholestane [34]. Multicomponent synthesis of steroid–thiazole hybrids from a steroidal ketone [36]. Synthesis of cholanic pseudo-peptide derivatives by novel MCRs based on the reactivity of ynamide [37][38]. Synthesis of steroid-fused pyrimidines and pyrimidones using the Biginelli

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• ternary heteroarylmethane-inspired hybrids by coupling diversely substituted indoles (Ar1) with quinoline aldehydes, quinolone aldehydes, chromone aldehydes, and fluorene aldehydes (Ar2CHO) and coumarins (Ar3) in 1:1:1 ratio by simple reflux in ethanol solvent to form the corresponding highly crowded tris

• synthesis of ternary heteroarylmethane-inspired hybrids is presented, by coupling quinoline aldehydes, quinolone aldehydes, chromone aldehydes, and fluorene aldehydes with substituted indoles and coumarins. The method enabled the synthesis of novel libraries of giant (Ar1Ar1Ar2)CH and (Ar1Ar2Ar3)CH triads 8

• -PF6 salt 10{4,4,8}. 1D- and 2D-based NMR assignments for methylium-PF6 salt 10{4,4,11}. Optimized geometry of methylium-PF6 salts 10{4,4,8}. Optimized geometry of methylium-PF6 salt 10{4,4,11}. Representative examples of tris(hetero/aryl)methanes, molecular hybrids and bis(indolyl)methanes with useful

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• pathogenic against humans, they are widely used as biocontrol agents in agriculture [9]. Natural products produced by bacteria play an important role in the bacteria/nematode/insect life cycle and most natural products are non-ribosomal peptides (NRP), e.g., rhabdopeptides [10][11] and polyketide–NRP hybrids