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

• -product biosynthesis and combinatorial solid-phase chemistry, this strategy has expanded the sequence space of macrocyclic peptides significantly (Scheme 2c). The daptomycins The calcium-dependent antibiotic (CDA, 11), daptomycin (12), and A54145 are acidic lipopeptides isolated from Streptomycetes, which

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

• , the combinatorial biosynthesis of diterpene pyrones, derived from a pyrone skeleton and a C20 terpenoid skeleton, has been achieved by combining multiple biosynthetic pathways in a fungal heterologous expression host [16]. First, subA (PKS), subC (PT), subD (GGPP synthase), subE (FMO), and subB (CYC

• combinatorial biosynthesis of diterpene pyrone meroterpenoids. The production of subglutinol A by SubABCDE + DpasF (A), the production of novel diterpene pyrones by SubABCDE + various tailoring enzymes (B), and the production of schearone A by SubACD + EsdpE + EsdpB (C). The biosynthetic reaction from the

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

• of several diseases [28][29][30]. They have also been applied in the field of materials science, especially for the synthesis of metal and covalent organic frameworks, dyes, hole-transporting materials and sensors, and in dynamic combinatorial chemistry [31], indicating a wide applicability

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• successful [25][26][27]. The only exception is the latest study by Cheng et al. who reported breakthrough findings in the development of highly potent and selective human GMII inhibitors. A combination of natural product-inspired combinatorial chemistry and computation-guided synthesis provided a nanomolar

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• synthesized with frequently occurring pharmacophores originating from drug components comes to the conclusion that the thioamide linkage establishes an intriguing class of biologically significant compounds amenable to combinatorial chemistry [43]. This organic functional group is found in vital biological

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• become a promising strategy for targeted discovery of natural products [10][11][12], which can also provide enzymatic tools toward combinatorial biosynthesis [13][14]. As terpene synthases play a fundamental role in constructing molecular skeletons, great efforts have been devoted to mining novel

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

• , parallel/combinatorial synthesis, multicomponent chemistry, metal-catalyzed coupling reactions as well as NMR, preparative/analytical liquid chromatography and mass spectrometry). – An improved understanding of molecular pharmacology along with in vitro or in vivo assays to detect various aspects of drug

• ][231]. Across the last 40 years, to address the fundamental issue of accessing new chemical entities, the industry expanded their collections by buying other pharmaceutical companies or via the synthesis/purchase of chemical libraries prepared for instance by combinatorial chemistry. If, initially, the

• combinatorial approach [232][233] appeared to have only led to one anticancer drug [234], major progresses in the design, selection, generation and purification of libraries have since then turned this type of chemistry into a central tool for drug discovery [235][236][237] along with more recent success

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• , Department of Microbial Bioactive Compounds, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, No. 185 East Lake Road, Wuhan, 430071

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• -supported combinatorial approaches [11][12][13]. The most relevant comparison of peptoids with peptides is in fact with polyprolines due to the presence of backbone tertiary amide linkages, much more prone to cis/trans equilibria than secondary amides. Indeed, in proteins, cis-amide bonds are most often

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• Siyu Wang Lianyou Zheng Shutao Wang Shulin Ning Zhuoqi Zhang Jinbao Xiang The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, P. R. China 10.3762/bjoc.17.167 Abstract A base- and catalyst-free C

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• , which results in a various number of tailored models [75][76][77], like the Flory–Huggins–van Santen (FHS) model. The FHS model shows that the combinatorial entropy of mixing is much smaller for macromolecules than for compounds with a low molar mass. For modelling of phase diagrams with LCST and/or

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

• )-glucosamine macrocyclic compounds [265]. The iterative glycosylation of N-Phth protected 2-deoxy-2-aminothioglycosides allowed for the combinatorial synthesis of short oligoglucosamines having β(1–6) and/or β(1–4)-linkages [263]. Automated solution-phase synthesis of β(1–6)-glucosamine oligosaccharides

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• reduction; there are many potential applications of this field in the small scale chemistry as well. For example, areas like combinatorial chemistry [33][34][35], complex multistep syntheses [14][36][37], synthesis of pharmaceutical substances have witnessed tremendous growth using flow chemistry approach

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• have not been considered here, from a de novo standpoint, owing to the combinatorial complexity that would arise from equal participation of the donors CMP-Neu5Ac, CMP-Neu5Gc, and CMP-KDN. Chemical structure of ganglioside GM1a (a β-ᴅ-galactosyl-(1→3)-N-acetyl-β-ᴅ-galactosaminyl-(1→4)-[α-N

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• mannose, Hex/H, 162.0528 Da), N-Acetylhexosamines (N-acetylglucosamine or N-acetylgalactosamine, HexNAc/N, 203.0794 Da), fucose (Fuc/F, 145.0579 Da), and sialic acid (N-acetylneuraminic acid, NeuAc/S, 291.0954 Da). The combinatorial possibilities of these building blocks and the variety of structural

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• mostly unstructured in solution, aptamers typically fold into their three-dimensional structure upon binding the respective target molecule [2]. Aptamers are normally identified by the in vitro selection from combinatorial libraries of nucleic acids [3]. In the past decades, interest in aptamers has

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• -interlocked catenanes. When both cages were mixed without C70, the dynamic combinatorial library (DCL) of seven compositionally distinct mixed-ligand Zn4L6 cages was observed (Figure 5b). An efficient self-sorting was only observed after the addition of the guest C70. As expected, the cage [Zn4(8')6]8

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• on the endosomal uptake and release. However, a better binding affinity to DNA does not necessarily mean a higher DNA transfection efficiency. As an example, two GCP-modified peptide tweezers 14 with nanomolar dissociation constants, identified by the high-throughput screening of a combinatorial

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• for peptides can be powerful tools for labeling or inhibition. Finding those binding motifs, especially in water which competes for intermolecular H-bonds, poses an enormous challenge. A dynamic combinatorial library can be a powerful method to overcome this issue. We previously reported artificial

• receptors emerging form a dynamic combinatorial library of peptide building blocks. In this study we aimed to broaden this scope towards recognition of small peptides. Employing CXC peptide building blocks, we found that cyclic dimers of oxidized CFC bind to the aromatic peptides FF and YY (K ≈ 229–702 M−1

• ), while AA binds significantly weaker (K ≈ 65–71 M−1). Keywords: artificial receptor; dynamic combinatorial chemistry; dynamic covalent chemistry; molecular recognition; thiolate–disulfide exchange; Introduction Peptides are one of the most abundant and structurally versatile motifs in nature. Thus

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• benign methodologies for the generation of structurally diverse triazinethione derivatives is still challenging in organic synthetic chemistry and medicinal chemistry. Multicomponent reactions (MCRs) gained much interest among synthetic organic chemists as well as in combinatorial chemistry and drug

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• with a bromoalkyne (Scheme 24) [39]. The catalyst was selected using a combinatorial approach for the selection of the optimal catalyst structure. The product was isolated in an excellent 87% yield. In 2018, Wang, Xu, and co-workers described the reductive decarboxylative alkylation of glycine and

• unusual sequence to functionalize molecules. Indeed, it relies on a redox transformation with a concerted proton and electron exchange. Note that this process can occur either through an oxidative or a reductive pathway [47][48][49]. In 2018, during the development of a combinatorial approach to select

• molecule through a transfer of energy to a second one. Then, this second molecule is raised to the excited state and can then react [51][52]. During the course of the design of a library of copper photocatalysts through a combinatorial approach, Collins and co-workers reported the copper-photocatalyzed

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• evolutionary advantage; even more so when combined with tailoring enzymes that have a broad substrate tolerance and catalyze multiple, sequential tailoring reactions [40]. This diversification process resembles the strategy embedded in the construction of combinatorial libraries by organic chemists to generate

• number of bacterial genome sequences available and the development of advanced bioinformatics tools, more type II/I diterpene TC tandems are likely to be discovered. By applying the same combinatorial concept, it is expected that the diterpene chemical space can be significantly expanded. Cytochrome

• step and then modified by tailoring reactions make terpenoid biosynthesis particularly amenable for generating non-natural variants through engineering. It is easy to imagine that the combinatorial pairing of promiscuous TCs and CYPs harbors great potential to achieve this goal, and the integration of

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2019, 15, 2753–2764, doi:10.3762/bjoc.15.266

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• combinatorial chemistry. This highlight article discusses the unusual properties of fulvenes and their varied cycloaddition chemistry, focussing on applications in organic and natural synthesis, dynamic combinatorial chemistry and materials chemistry, including dynamers, hydrogels and charge transfer complexes

• reactivity and mechanisms of action. Dynamic combinatorial chemistry Dynamic combinatorial chemistry (DCC) is an emerging field with promising applications in drug discovery. DCC involves the generation of new molecules via reversible reactions of simple building blocks, referred to as a dynamic

• combinatorial library (DCL). As the reactions are reversible, several different structures are possible and the system exists in equilibrium. Upon the addition of an external surface (binding target), the equilibrium is altered and the product most stabilised through surface binding is amplified. Under optimal

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• Xiang Sun You-Sheng Cai Yujie Yuan Guangkai Bian Ziling Ye Zixin Deng Tiangang Liu Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, P. R. China 10.3762/bjoc.15.202 Abstract Sesquiterpene