New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• , anti-inflammatory [28][43], antiviral [39][44], antidiabetic [45] effects and cancer cell growth-inhibitory features should be mentioned [29][46][47][48]. Ugi-4CR has been applied in the synthesis of natural products, as bicyclomycin, furanomycin, penicillin etc. [53]. The high combinatorial potential

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• , combinatorial enzyme design and microbial engineering. Mutational engineering of terpene synthases Site-directed mutagenesis of diterpene cyclases is conventionally applied to elucidate structure–function relationships and mostly targets the active site of the enzyme in order to change the polarity or dimension

• mutations of MvCPS1, W323L:F505Y, and W323F:F505Y completely changed the product specificity towards a novel, so far uncharacterized halimadane type diterpene [58] (Scheme 2). Combinatorial biosynthesis – enzyme design for manufactured terpenes Conventional identification of new enzyme activities involved

• performed in vivo substrate promiscuity tests following a combinatorial approach [41][66]. The resulting products entailed pimarane- and abietane-type diterpenes as well as the trans-clerodane type diterpene kolavenol, a putative intermediate in the salvinorin A biosynthesis. Other bifunctional diterpene

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• the application in parallel synthesis and combinatorial chemistry. Experimental Typical procedure for the GBB multicomponent reaction. To a solution of 2-aminopyridine (1a, 0.5 mmol), 2-ethynylbenzaldehyde (2a, 0.5 mmol), and tert-butylisocyanide (3, 0.6 mmol) in 1 mL of methanol were added p

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• procedure on solid support [3][24][25]. These improvements enabled, for the first time, the synthesis of a combinatorial library of all possible N-methylated analogues of a given sequence [26]. These strategies have been used over two decades as standard procedures for N-methylations of linear and cyclic

Conjecture and hypothesis: The importance of reality checks

• David Deamer

Beilstein J. Org. Chem. 2017, 13, 620–624, doi:10.3762/bjoc.13.60

• mononucleotides [22][28][29]. Because the resulting polymers can be encapsulated in lipid vesicles, it has been proposed that the resulting protocells are candidates for combinatorial selection and the first steps of evolution [30]. Conclusion From the above discussion, alternative conjectures have been published

• present in the mixture, the conditions will allow them to assemble into membranous compartments. A plausible physical mechanism can produce encapsulated polymers in the form of protocells and subject them to combinatorial selection. These conditions can also be considered to be predictions, because each

A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

• Arno Verlee,
• Thomas Heugebaert,
• Tom van der Meer,
• Pavel I. Kerchev,
• Frank Van Breusegem and
• Christian V. Stevens

Beilstein J. Org. Chem. 2017, 13, 303–312, doi:10.3762/bjoc.13.33

• suitable for automation, thus allowing the fast synthesis of compound libraries, but as opposed to, e.g., combinatorial chemistry, the developed protocols are directly useful for scale-up. A class of small molecules where these principles can apply for are m-sulfamoylbenzamides. These compounds proved to

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• the sample is injected directly into the flow probe to give a simple flow-NMR system. Applications of DI–NMR include combinatorial chemistry for the analysis of libraries [36], analysis of biofluids for clinical diagnosis [37] and metabolomics [38]. Applications in organic synthesis In this section we

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• energy consumption and hence lead to more effective and sustainable processes [4][5][6]. MCRs found numerous applications, i.e., in combinatorial chemistry, target oriented synthesis or polymer science [6][7][8]. The most important MCRs are the Strecker amino acid synthesis (1850), the Hantzsch

Construction of bis-, tris- and tetrahydrazones by addition of azoalkenes to amines and ammonia

• Artem N. Semakin,
• Aleksandr O. Kokuev,
• Yulia V. Nelyubina,
• Alexey Yu. Sukhorukov,
• Petr A. Zhmurov,
• Sema L. Ioffe and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2016, 12, 2471–2477, doi:10.3762/bjoc.12.241

• hydrogen and carbon atoms attached to it [62]. Conclusion In conclusion, we developed a convenient approach for the synthesis of hitherto unknown poly(hydrazonomethyl)amines I from α-haloketones, hydrazides and simple amines (ammonia). Using this combinatorial approach, a series of new prospective bis

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• peptide-based disulfide macrocycles in a dynamic combinatorial library [49]. They observed different product distributions when reaction mixtures were shaken than when stirred, concluding that “mechanical forces can ... determine the outcome of a covalent synthesis” and that the ‘mechanosensitivity’ of

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• clearly shows that such a combination of fragments is entirely predictable on the basis of a simple combinatorial analysis that does not violate mechanistic requirements when these fragments come together in an electophilic and nucleophilic sense. The discovery of reaction conditions that experimentally

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• cycloaddition one of the most valuable means of combinatorial chemistry. Such multicomponent reactions are characterized by productivity, operational simplicity, and efficiency [9][10][11][12][13]. A highly interesting class of heterocycles which is accessible through 1,3-dipolar cycloaddition reactions are

Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• Hui Hong Yuhui Sun Yongjun Zhou Emily Stephens Markiyan Samborskyy Peter F. Leadlay Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, United Kingdom Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University, Ministry of Education

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• Zeynep Kanlidere Oleg Jochim Marta Cal Ulf Diederichsen Institute of Organic and Biomolecular Chemistry, Georg-August University Göttingen, Tammannstrasse 2, D-37077 Göttingen, Germany 10.3762/bjoc.12.203 Abstract Dynamic combinatorial chemistry (DCC) is an attractive method to efficiently

• analogue. Keywords: base-pairing; base-pair mismatch; DNA functionalization; DNA templates; dynamic combinatorial chemistry; D-threoninol based scaffolds; Introduction The well-defined duplex structure, self-assembling by base-pair recognition, and the accessibility by solid-phase synthesis make DNA

• metal ligands or fluorophores. Functional molecules of interest can be tethered post-synthetically in an irreversible manner as amide or reversibly as imine or thioester. Recent advances in dynamic combinatorial chemistry [29][30][31][32][33][34][35][36][37][38][39][40] have enabled the utilization of

New furoisocoumarins and isocoumarins from the mangrove endophytic fungus Aspergillus sp. 085242

• Ze’en Xiao,
• Senhua Chen,
• Runlin Cai,
• Shao’e Lin,
• Kui Hong and
• Zhigang She

Beilstein J. Org. Chem. 2016, 12, 2077–2085, doi:10.3762/bjoc.12.196

• District, Shenzhen, 518102, China Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education of China, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China 10.3762/bjoc.12.196 Abstract The chemical investigation of the mangrove endophytic fungus Aspergillus

Synthesis and NMR studies of malonyl-linked glycoconjugates of N-(2-aminoethyl)glycine. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger,
• Sven Hafner and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 1939–1948, doi:10.3762/bjoc.12.183

• Markus Norrlinger Sven Hafner Thomas Ziegler Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany 10.3762/bjoc.12.183 Abstract Four glycoconjugate building blocks for the construction of combinatorial PNA like glycopeptide libraries were

From supramolecular chemistry to the nucleosome: studies in biomolecular recognition

• Marcey L. Waters

Beilstein J. Org. Chem. 2016, 12, 1863–1869, doi:10.3762/bjoc.12.175

• -helices; aromatic interactions; β-hairpin peptides; cation–π interactions; dynamic combinatorial chemistry; histone; molecular recognition in water; nucleosome; π–π-stacking; post-translational modification; supramolecular chemistry; Review Childhood influences When thinking about how to start writing

• work of Jeremy Sanders and co-workers on dynamic combinatorial chemistry (DCC) while being a graduate student and postdoc (Figure 7) [42][43]. Like folded peptides that self-assemble into their functional state, DCC allows molecules to self-assemble in the presence of a template. Moreover, DCC is

• asymmetric dimethylarginine (aDMA, cyan). (d) Computational model of a synthetic receptor, A2D (green), bound to aDMA (cyan) [41]. Dynamic combinatorial chemistry [41][42]. Acknowledgements I gratefully acknowledge funding from the NSF, NIH, DTRA, and W. M. Keck Foundation over the years. I am also indebted

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• combinatorial biosynthesis has to be further evaluated in the future. Selected monocyclic and monobenzo α-pyrone structures. The basic core structure of dibenzo-α-pyrones. Selected dibenzo-α-pyrones. Structure of ellagic acid and of the urolithins, the latter metabolized from ellagic acid by intestinal bacteria

Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

• H. Surya Prakash Rao and
• A. Veera Bhadra Rao

Beilstein J. Org. Chem. 2016, 12, 496–504, doi:10.3762/bjoc.12.49

• further step with a variety of aryl boronic acids), it should be possible to provide a unique opportunity for the modular synthesis of unsymmetrical triarylmethanes. If successful, the method could provide an opportunity for the synthesis of a combinatorial library of the coveted molecules. Herein, we

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• electronic tongue and chemometrics were methods to differentiate ATP, GTP and AMP [92], phosphorylated peptides [93], as well as a technique to identify sweeteners in coffee and tea [94]. Each of these studies used combinatorial libraries of peptides around a preorganized scaffold or with a known targeting

• our group are on wines. As with our earlier work, the approach uses a suite of combinatorial peptides as differential receptors. The peptides are biased with a large fraction of the amino acid histidine, are metallated with Cu, Ni, and Zn, and bind indicators to create a series of IDAs that can

• our citrate receptor [63][64][65][66][67]. Combinatorial peptide library designs used for differential sensing purposes [92][93][94]. Concept behind the electronic tongue, with micromachined divets that hold beads placed in an array. While not micromachined, a much simpler analog that accomplishes

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• companies eliminated their natural product research during the past decades due to diminishing returns from this discovery platform. Instead they intensely focused on screening efforts and combinatorial chemistry to find and develop novel drug candidates. This approach of target-focused screening of

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• partner such as cis-1,4-diacetoxy-2-butene may statistically prevent the formation of 80 thus allowing the CM to occur. In 2010, Harding et al. attempted to use reversible aqueous metathesis for the construction of a dynamic combinatorial library aimed at identifying DNA ligands [76]. Toward that goal

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• esterifications of sugars and steroids, using acylating agents different from simple aliphatic acids [7][8][9]. Specifically, years ago Dordick and coworkers proposed the so-called ‘combinatorial biocatalysis’ as an approach to easily produce small libraries of derivatives of bioactive natural compounds using a

Is organic chemistry science – and does this question make any sense at all?

• Andreas Kirschning and
• Thomas A. C. Reydon

Beilstein J. Org. Chem. 2015, 11, 893–896, doi:10.3762/bjoc.11.100

• conditions (molecular recognition, self-assembly and dynamic combinatorial chemistry) and how their molecular composition would be; the question why nature developed DNA and RNA that utilize ribose and 2-deoxyribose as central nucleotide building blocks instead of the more abundant and readily available

Influence of length and flexibility of spacers on the binding affinity of divalent ligands

• Susanne Liese and
• Roland R. Netz

Beilstein J. Org. Chem. 2015, 11, 804–816, doi:10.3762/bjoc.11.90

• dissociation constant for each ligand times the probability that the spacer bridges the two binding pockets. A detailed derivation of the dissociation constants is presented in Supporting Information File 1. Furthermore, Figure 1b summarizes the combinatorial factors for each binding mode that count the number