Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• for ricin toxin A (RTA) inhibitors [14]. By deprotonation of the lactam NH, and conversion to the DBU salt, the pterin easily dissolves in methanol at high concentrations, unprecedented for unfunctionalized pterins. This greatly accelerated the development of a library of bioactive pterins, as it

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

• 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

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• in excellent yields by reacting the protected ligands 135 with DABCO [111][112]. A diverse library of ligands prepared in a similar manner can be obtained by varying the phosphine and the substituents around the skeleton. Some of the ligands prepared include compounds 137–140 shown in Figure 3 [111

• presents the syntheses and architectures of phosphine N-heterocyclic ligands. Despite their success and many reported P,N-phosphine ligands, there is a need to designed new compounds to increase their library and to investigate other applications. It can be foreseen, that more probing and research on

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• this methodology, they assembled a library of compounds in good to excellent yields, with just 1 mol % of the photoredox catalyst 11 required. They observed that the yields of the products were dependent on various factors, such as the redox potential of the catalyst, the electronics of the ligand, and

• substituents (Scheme 5), and (v) the rate-determining step (i.e., breaking of the C–H bond) was suggested to follow a first-order kinetic isotope effect (KH/KD = 5). As such, a library of benzothiazole derivatives was reported using this methodology, and a plausible mechanism is shown in Figure 9. Synthesis of

• previously reported methods required high temperatures [118][119][120]. A library of compounds was reported by that group using this approach, and a plausible mechanism is shown in Figure 13. Arylation of purines: Purine bases and purine nucleosides, which are common structural motifs in DNA and RNA, have an

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• photoswitchable analogue 2 in an allograft mouse model, the first in vivo photopharmacology application for a DAE-derived peptide as an anticancer agent has been demonstrated [29]. In order to optimize 2, we have recently performed a structure–activity relationship (SAR) study using a library of photoswitchable

• derivatives of 2 [30]. The library contained 29 compounds grouped into several series: with natural amino acid mutations affecting the amphipathicity (series i), with point mutations that modulate polarity and conformational stability of the β-structural elements (series ii), with backbone N-alkylation and

• values were practically identical in 3 independent experiments, both assays were used to evaluate the entire library of 19 photoswitchable peptides (see Table 2). Overall, the two assay versions gave comparable LD50 values for each of the tested peptide, namely LD50(open)1h vs LD50(opened)1h, and LD50

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• ]pyridine ring has been synthesized via the microwave-assisted Mizoroki–Heck reaction. The efficient modification of the imidazo[1,2-a]pyridine ring has been achieved as late-stage functionalization, enabling and accelerating the generation of a library of compounds from a common precursor. Keywords: α

• overrated [1]. However, as is true for many reactions, the late-stage functionalization of target compounds or their advanced intermediates is rarely an extension of reaction conditions developed for structurally simple analogs. The late-stage approach is especially desirable in the synthesis of a library

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• , N9B 3P4, Canada, Department of Chemistry, Oakland University, 146 Library Drive, Rochester, Michigan 48309-4479, USA 10.3762/bjoc.16.1 Abstract Dicobalt hexacarbonyl nucleoside complexes of propargyl ether or esters of 5-substituted uridines react with diverse C-nucleophiles. Synthetic outcomes

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• sialylations at the C-2 position can be conducted. To study substrate specificity of bacterial and human sialidases using the library of position C-7-modified Neu5Ac, Chen and co-workers have described the systematic substitution of the OH-7 moiety of Neu5Ac by F, OMe, H, and N3 substituents [20]. Additionally

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• relatively small structural changes to probe the biosynthetic machinery: the native sequence ᴅ-alanine-dehydroalanine-sarcosine was varied in a small library by replacing dehydroalanine (Dha) with ᴅ- or ʟ-alanine and sarcosine with glycine (Figure 3). The synthesis of these biosynthesis analogs 9–14 was

• that one or more of the biosynthetic proteins are not active under the applied conditions. Experimental details are provided in Supporting Information File 1. Conclusion In summary, we have designed and successfully synthesized a library of tripeptide thioesters for the use in the mutasynthesis of

• argyrin derivatives. In the initial strategy, the sequential synthesis of the peptides followed by activation as a SNAc ester successfully yielded five out of six desired library members. Following this strategy, the mutasynthon carrying the native sequence ᴅ-Ala-Dha-Sar could not be transformed into the

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

• -isozizaene (33) synthase mutants that produce different sesquiterpene skeletons. Substrate promiscuity and engineering of CYPs. a) Selected examples from using a CYP library to oxidize various monoterpenes. b) Rational engineering of P450BM3 for epoxidation of amorphadiene (21). F87A/A328L and R47L/Y51F

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• . Pharmacokinetic studies in mouse showed CNS penetration of 1 is very low with a brain/plasma concentration ratio of just 0.01. A small library of amides 17 were prepared from acid 1 to explore if 1 could be modified to deliver a CNS penetrant tool by capping off the acid as an amide. Although significant Notum

• brain tissue. Amide analogues of 1 to explore CNS penetration and future opportunities With a peripherally restricted control in hand, we elected to explore if 1 could be modified to deliver a CNS penetrant tool by capping off the acid as an amide. A small library of amides 17 were prepared from acid 1

• . The full PK data set is presented and shared as ‘open data’. This complete data set (along with others) will also assist with the creation of improved predictive pharmacokinetic models. A small library of amides 17 were prepared from acid 1 to explore if 1 could be modified to deliver a CNS penetrant

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• remained consistent despite variations to the carbon and nitrogen sources across agars and liquid media, but the productivity was superior on grains, notably rice and barley. A search of the UV–vis profiles against our in-house library of type species (>25,000 spectra from 2,000 species, including 205

• library (>7,100 standards) also failed to provide a single known secondary metabolite, further suggesting the strain was a hitherto unaccounted species of Aspergillus. A. nanangensis was cultivated separately on jasmine rice and pearl barley for 21 days, which resulted in confluent and thick mycelial

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• inhibitors has already been fruitful in the past [32][33]. Therefore, a focused kinase inhibitor library from GlaxoSmithKline was screened for biological activity on human sirtuin isoforms Sirt1–Sirt3. Aza-stilbene derivative GW435821X (2a, Figure 1), initially published as c-RAF kinase inhibitor, was

• difficulties [64]. Conclusion Based on lead structure GW435821X (2a) a small library of analogous azastilbene compounds was designed, synthesized and tested for their inhibitory activity against the human sirtuin isoforms Sirt1, Sirt2 and Sirt3. Compared to the lead structure the inhibitory potency could be

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 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

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries

• Xiao Xie,
• Michela Zuffo,
• Marie-Paule Teulade-Fichou and
• Anton Granzhan

Beilstein J. Org. Chem. 2019, 15, 1872–1889, doi:10.3762/bjoc.15.183

• Xiao Xie Michela Zuffo Marie-Paule Teulade-Fichou Anton Granzhan CNRS UMR9187, INSERM U1196, Institut Curie, Université Paris Sud, Université Paris Saclay, Bât. 110, Centre universitaire Paris Sud, F-91405 Orsay, France 10.3762/bjoc.15.183 Abstract A library of 52 distyryl and 9 mono-styryl

• and quantum yield, low background fluorescence) are still poorly understood, mostly due to the lack of comparative studies. To explore this aspect, we report the synthesis and systematic study of a library of 61 di- and mono-styryl dyes, as potential “light-up” probes for G4 structures. The study aims

• at the improvement of photophysical properties of the dyes and the establishment of structure–properties relationships. Results Design and synthesis of the dye library On the basis of the previously established distyryl scaffold, we designed 49 novel derivatives through systematic variation of the

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• -2-carbaldehyde on the other hand resulted in appreciable yields under similar reaction conditions. The authors have successfully constructed a big library of 28 compounds with varying structure. In 2013, Gao et al. have exploited the TM-catalyzed nucleophilic addition reactions of haloalkynes 5

• synthetic cycles without loss in activity. In addition to this, TiO2 is more stable, abundant, nontoxic, and economical [102]. Out of different supports examined like Al2O3, ZrO2, CeO2, SiO2, Al-Ti, OMS-2, C, etc., TiO2 was found to be the best for this transformation. Furthermore, a library of compounds

• product. This was an unprecedented report for the synthesis of a library of targeted moieties using a nano-click catalyst. The triazole precursor was also synthesized by the group using nano-copper oxide in an aqueous medium. The reaction has well tolerated variedly substituted starting materials whether

A heteroditopic macrocycle as organocatalytic nanoreactor for pyrroloacridinone synthesis in water

• Piyali Sarkar,
• Sayan Sarkar and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2019, 15, 1505–1514, doi:10.3762/bjoc.15.152

• synthesis of diversely functionalized pyrroloacridinones in aqueous medium. A library of compounds was synthesized in a one-step pathway utilizing 10 mol % of the nanoreactor following a sustainable methodology in water with high yields. Keywords: heteroditopic macrocycle; organocatalyst; nanoreactor

• summary, a multifunctional heteroditopic macrocycle is established as an efficient nanoreactor for organic transformations in water. Using this macrocycle, a library of biologically interesting highly substituted pyrroloacridines has been synthesized with high yields from easily available starting

Selective detection of DABCO using a supramolecular interconversion as fluorescence reporter

• Indrajit Paul,
• Debabrata Samanta,
• Sudhakar Gaikwad and
• Michael Schmittel

Beilstein J. Org. Chem. 2019, 15, 1371–1378, doi:10.3762/bjoc.15.137

• quantitative interconversion is the result of a delicate double self-sorted transformation requiring orthogonality of two heteroleptic complexation motifs (HETPYP-I and hetero-sandwich complexation at DABCO). Within a selected library of binding guests, DABCO is the only one effecting the interconversion. Due

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• available starting materials including scaffold diversity. A small focused compound library of 23 Ugi products was created and screened for antibacterial activity. Keywords: antibacterial activity; Doebner reaction; pyrazolo[3,4-b]pyridine carboxylic acids; Ugi reaction; Introduction Modern medicinal

• efficient procedure for the synthesis of compounds 11a–q through reaction of aromatic aldehydes 8a–d, amines 9a–f, tert-butylisocyanide (10) and heteroaromatic carboxylic acids 4a,b in a 2:1 mixture of methanol and DMF at 70 °C. Following this procedure, a small library of seventeen Ugi products was

• obtained (Table 1). Next, we applied pyrazolo[3,4-b]pyridine-6-carboxylic acid 7b with another positional location of the substituents in comparison with compounds 4 in the Ugi reaction with the same reagents 8, 9 and 10 using the optimized procedure (Table 1). This expanded the library of Ugi products by

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

• protocol provided a small library of steroidal 2,5-diketopiperazines 6 obtained as a single diastereomer, thus proving the high diastereoselection of the initial Ugi-4CR with the steroidal carbonyl substrate. In the 2,5-diketopiperazine ring, the configuration of the new asymmetric center C-3’ was S, a

• substitution pattern at the phenyl moiety (Figure 2A). The small library of compounds enabled a better understanding of the structural factors determining the antiviral activity versus the cytotoxic one, with the major effect found for substituents at the para-position [23]. Eventually, this work allowed the

• library of androstanic derivatives 21 (Figure 2B) and their reduced analogues bearing the 3β-hydroxy group were biologically tested showing antifungal activity against Fusarium virguliforme and Fusarium solani. The generation of this compound library suffered from the formation of the Passerini reaction

A three-component, Zn(OTf)₂-mediated entry into trisubstituted 2-aminoimidazoles

• Alexei Lukin,
• Anna Bakholdina,
• Anna Kryukova,
• Alexander Sapegin and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103

• preparation of ureas 4 could, in principle, enable a three-component entry to imidazoles 5 (an attractive option from the standpoint of library array synthesis), we compared the isolated yield of the above reaction (with the ready-made urea 4a) with the yield obtained in the three-component format. To our

• which makes it a useful tool for library array synthesis. The investigation of other metal-catalyzed transformations of propargylureas is underway in our laboratories and will be reported in due course. Examples of imidazole (1 and 2) and oxazole (3) syntheses from propargylamides previously reported

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• synthesis pathway involving a diastereoselective hydroboration towards (aryltriazolyl)methyl galactopyranosyl derivatives and determined the viability of this as a scaffold for galectin inhibitors by screening a library of fourteen different products against galectins -1, -3, -4C (C-terminal CRD), -4N (N

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• library of aldehydes (aromatic: 97–99% ee; aliphatic: 84–98% ee) [28]. Thereafter, many different kinds of hydrogen bonding-based organocatalysts have been developed for oxo-DA reactions [29][30][31][32][33][34][35]. One kind of organocatalyst in particular, which is based on an oxazoline template with

Halogen bonding and host–guest chemistry between N-alkylammonium resorcinarene halides, diiodoperfluorobutane and neutral guests

• Fangfang Pan,
• Mohadeseh Dashti,
• Michael R. Reynolds,
• Kari Rissanen,
• John F. Trant and
• Ngong Kodiah Beyeh

Beilstein J. Org. Chem. 2019, 15, 947–954, doi:10.3762/bjoc.15.91

• , Finland Oakland University, Department of Chemistry, 146 Library Drive, Rochester, Michigan, 48309-4479, USA 10.3762/bjoc.15.91 Abstract Single crystal X-ray structures of halogen-bonded assemblies formed between host N-hexylammonium resorcinarene bromide (1) or N-cyclohexylammonium resorcinarene

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• combination of two isocyanide-based multicomponent reactions (azido-Ugi and Passerini reactions) allowed easy access to a library of macrocyclic depsipeptides in only four steps with variations in the size of the macrocycle as well as in the side chains (Scheme 15). This was the first example in which the

• has been found in the use of dynamic combinatorial chemistry (DCC) [42]. One of the most accessible reversible bonds is the imine bond and has been widely used in DCC. In this context, a freezing process of a dynamic combinatorial library (DCL), which is a system of recognition and thermodynamic