Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• -phosphonodepsitetrapeptides 58 as inhibitors of the aspartic peptidase pepsin. Synthesis of a β-phosphonodepsidipeptide library 64. Synthesis of another β-phosphonodepsidipeptide library. Synthesis of γ-phosphonodepsidipeptides. Synthesis of phosphonodepsipeptides 85 as folylpolyglutamate synthetase inhibitors. Synthesis of

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• characterization facility at CSIRO Manufacturing in Melbourne Australia. This can generate and test hundreds of polymers, nanomaterials, catalysts, or metal organic frameworks in a day. Clearly, certain types of chemistries (benzodiazepines, click reactions, etc.) are amenable to large chemical library synthesis

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

• attracted broad attention in the field of organic synthesis [40][41][42]. In order to expand the structural diversity of GBB products, further investigation of GBB-based synthetic strategies remains highly desirable. In continuation of our research on the development of MCR strategies for the rapid library

• synthesis of biologically interesting heterocycles [43][44][45][46][47], we were interested in a practical synthetic strategy towards imidazo[1,2-a]pyridine-fused isoquinoline systems. We believe that this type of polycyclic systems may have interesting biological profiles [48]. Herein, we report our recent

Continuous-flow synthesis of highly functionalized imidazo-oxadiazoles facilitated by microfluidic extraction

• Ananda Herath and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2017, 13, 239–246, doi:10.3762/bjoc.13.26

• less attractive during scale-up due to the difficulty of removal of these solvents during purification. Consequently the current method is limited to small scale library synthesis. Therefore, our next goal was to convert this microfluidic procedure to a sequence that would deliver compounds on a larger

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• -ethynylbenzamides 1 [35]. The rationale of our choice is based on molecular docking data. Using the published structure of the MDM2–p53 binding site, we have employed computational methods and focused library synthesis based on the isoindolinone template, to develop compounds with inhibitory activity. These studies

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• high efficiency and simple operation will make it have potential applications in the compound library synthesis. Experimental Typical procedure for multicomponent reaction. To a solution of isatin (3, 1.0 mmol), 2-aminopyridine (2, 1.35 mmol) and isocyanide (4, 1.35 mmol) in 4 mL of n-butyl alcohol was

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• ]. The synthesis of a small collection of imidazo[1,2-a]pyridine derivatives was realised through the application of different scavenger resins for in-line purification as well as a number of liquid handlers to orchestrate the library synthesis effort (Scheme 24). Using this semi-automated process a

Anionic sigmatropic-electrocyclic-Chugaev cascades: accessing 12-aryl-5-(methylthiocarbonylthio)tetracenes and a related anthra[2,3-b]thiophene

• Laurence Burroughs,
• John Ritchie,
• Mkhethwa Ngwenya,
• Dilfaraz Khan,
• William Lewis and
• Simon Woodward

Beilstein J. Org. Chem. 2015, 11, 273–279, doi:10.3762/bjoc.11.31

• rapid access to mono sulfur-containing acenes, and is applicable to small scale library synthesis. Only low cost reagents are required and otherwise difficult to synthesise hindered 1,3,4,12-tetrasubstituted species can be made straightforwardly. Use of bis-allene intermediates 2 for rapid access to

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• afforded an initial product Ph-CH(NH2)-CN of configurational instability[5]. In the following, Sigman and Jacobsen used a parallel combinatorial library synthesis for the discovery and optimization of a chiral catalyst for the reaction of imines and HCN [6]. From then on, various catalytic asymmetric

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• compounds 49 was obtained for antibacterial screening. In this report, 5'-azidothymidine or 5'-azido-2'-deoxyuridine was linked to a polystyrene butyldiethylsilane resin and subsequently reduced to the polymer-supported thymidinyl (R = CH3) or 2′-deoxyuridinyl (R = H) aminonucleoside 47. The library

• synthesis was executed in 96-well plates, with one of the two amines 47, 12 carboxylic acids, 8 aldehydes, and an isocyanide per plate. The products 49 were cleaved from the support with HF/pyridine in THF. As expected, the Ugi products 49 were obtained as ca. 1:1 mixtures of diasteroisomers (based on HPLC

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• throughput; library synthesis; Introduction Amphiphilic compounds contain a hydrophilic polar head group and a hydrophobic non-polar side chain. Upon addition of water, these amphiphiles may self-assemble into lyotropic phases that have a variety of uses, from simple household detergents and cleaning

• completion. Attempts to synthesise amphiphiles using the C13 (19) and C15 (20) triple-chain tails failed, as these compounds did not dissolve readily under the library synthesis reactions conditions. When comparing double and triple-chain amphiphiles, the results are similar. Excellent yields are observed

Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

• Richard J. Ingham,
• Claudio Battilocchio,
• Joel M. Hawkins and
• Steven V. Ley

Beilstein J. Org. Chem. 2014, 10, 641–652, doi:10.3762/bjoc.10.56

• chemistry processes for synthesis. Automated procedures can have a significant impact on productivity, not just for traditional applications such as library synthesis, but also for one-off protocols for which automation may previously have required a much greater time investment. Raspberry Pi® (RPi

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• product formation and greener characteristics than the previous one in many respects such as (a) a less laborious and more step-economical reaction for the library synthesis of pyrrole-fused isocoumarin derivatives, since the starting materials dihydroxy indenofurans 6 and 7 need only one step for

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• , Germany 10.3762/bjoc.8.206 Abstract A three-component method for the synthesis of γ-lactams from commercially available maleimides, aldehydes, and amines was adapted to parallel library synthesis. Improvements to the chemistry over previous efforts include the optimization of the method to a one-pot

• parallel library synthesis. Improvements to the chemistry over the previous method include the introduction of asymmetry in the form of an organocatalyzed Michael addition, the removal of the main by-products and excess reagents by using an aqueous acid wash, and the optimization for a one-pot process

• . These efforts allowed the efficient use of automation for parallel library synthesis, culminating in the preparation of a library of 169 γ-lactams. Experimental General All single-vessel reactions were performed under an argon atmosphere in flame-dried glassware. The glass syringes and stainless-steel

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• chemical library synthesis. Thus, we chose to investigate the Pd-catalyzed benzylic substitution reaction of (coumarinyl)methyl acetates with various nucleophiles. In the forthcoming sections, the coupling of this coumarin template to arylboronic acids [56][57][58][59][60][61], amines [47] and

• because this approach could easily lead to rapid library synthesis. As aminomethylcoumarins are a biologically active chemical motif [6][7][8][9][10][11][12][13][14][15], we set out to produce a 128-member library of aminated coumarins using our method, with the goal of making unique, biologically active

• dialkylamines, cyclic and heteroatom-containing amines were utilized. Amines with various functional groups, such as amides, aromatics, olefins, and alkyne substitution patterns, were also incorporated in this library. The automated library synthesis had a success rate of >85%, with the desired products

Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• converted to the indoles. As yields and purities were found to be higher when −40 °C and 3 equiv of Grignard reagents were used, we adopted these conditions for our library synthesis. Functional groups such as halides were tolerated. Two exceptions were the hydroxycarboxylic acids 1{f},1{j} and the

Synthesis of a library of tricyclic azepinoisoindolinones

• Bettina Miller,
• Shuli Mao,
• Kara M. George Rosenker,
• Joshua G. Pierce and
• Peter Wipf

Beilstein J. Org. Chem. 2012, 8, 1091–1097, doi:10.3762/bjoc.8.120

• commercially available or easily prepared starting materials and creates many opportunities for further functionalization and chemical library synthesis. For example, a ring-closing metathesis of the alkene addition product affords structurally novel tricyclic isoindolinones with a newly formed seven-membered

• ring [19]. We have now developed this concept further toward a library synthesis of functionalized azepino-isoindolinone derivatives. Results and Discussion N-Alkylation of phthalimide with 4-penten-1-ol under Mitsunobu conditions, followed by NaBH4 reduction and pivaloate protection of the

• . Relative energies of alkene isomers based on RB3LYP/6-311G* calculations with MacSpartan ’06. X-Ray structure of epoxyalcohol 6. Amine building blocks for library synthesis. X-ray structure of amino alcohol 10{7}. Formation of isomerized azepinoisoindoline 3 and oxirane 5. Ring-closing metathesis of diene

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• protein–protein interactions. Keywords: chemical diversity; Huisgen cycloaddition; library synthesis; peptidomimetics; solid phase synthesis; triazole; Introduction The α-helix was the first-described secondary structure of peptides discovered by Linus Pauling in 1951 [1]. With about 30% of the amino

• [2 + 3] cycloadditions of resin bound azide 7 with five terminal alkynes. Compounds 13, with the exception of 13f, were only characterized during compound library synthesis, by HPLC–MS analysis. Ruthenium-catalyzed [2 + 3] cycloadditions of resin-bound azide 7 with three disubstituted alkynes

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• the perspective of library synthesis. First, easy access exists to a wide selection of commercially available or easily synthesized starting materials, i.e., isatins, propargylic and homopropargylic amines and alcohols. Second, three easily modifiable diversification sites, R1, R2 and R4, can be built

• reactions required the same amount of time (24 h) to achieve complete conversions, indicating that the presence of amidation catalyst Zr(Ot-Bu)4 in the one-pot two-step sequence had no effect on the cycloaddition of 13a. For the library synthesis, the two-step sequence was adopted in order to isolate the

• linkages showed significantly less reactivity in cycloadditions compared to those with amide linkages. The longer tether length also led to a decrease in cycloaddition reactivity. This chemistry was subsequently applied to a library synthesis, producing a focused library of eighty-eight members. Diversity