Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• and technologies [21][22][23][24][25][26][27][28][29][30]. Thus, numerous multistep total syntheses of organic compounds, including bioactive molecules [31][32][33][34][35] and natural products [36][37], have been performed in a highly chemo- and stereoselective manner through metathesis routes [38

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• inhibition activities comparable to that of panobinostat. Multistep syntheses afforded the visualized targets TOI1, TOI2, TOI3-rev and TOI4 whose biological evaluation confirmed the strength of HDAC8 inhibition with TOI4 displaying the greatest efficacy at varying concentrations. The results of this study

• developing single agent therapeutic hydroxamate derivatives, we began the synthesis of four leading HDAC8 diazine-based HDACis: TOI1, TOI2, TOI3-rev and TOI4 (Figure 1). Herein, we provide a summary of the design process followed by an outline of the multistep synthesis and preliminary biological evaluation

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• counterparts has received less attention. Current methodologies for the synthesis of acyclic mixed enol phosphonates include the Perkow-type reaction between phosphonites and α-halocarbonyl compounds [11], the mercury-catalyzed addition of phosphonic acid monoesters to terminal alkynes [12][13] and multistep

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• ], and borylation [32]), has been in great demand recently rather than the conventional multistep synthesis with nucleophilic substitution/cross-coupling via halogenation of BODIPYs [33] or from the activated precursors [34] via unstable pyrrolic intermediates. In particular, halogenation (e.g

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

• loss of catalytic activity. Using a multistep solid-phase procedure, Shantz et al. reported on SBA-15 functionalized with melamine-based dendrons (Scheme 3) [27]. The Cu and Cu/Au nanoparticles were then supported on this new composite to generate a nanocatalyst. The catalytic application of this

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• , Dept. of Chemistry, Technical University of Munich (TUM), Lichtenbergstr. 4, 85748 Garching, Germany 10.3762/bjoc.16.7 Abstract Terpene cyclases are responsible for the initial cyclization cascade in the multistep synthesis of a large number of terpenes. CotB2 is a diterpene cyclase from Streptomyces

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• hydroxy ester 4 followed by reaction with acetonitrile (CH3CN), a multistep approach would be less economical in industry (Scheme 1). Results and Discussion To date, the most economically appealing conditions from an environmentally friendly perspective entail relatively mild base-promoted (potassium tert

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

• significantly (Figure 8) [98]. Despite difficulties in engineering terpene biosynthesis, total synthesis of complex terpenoids does not appear to be a viable alternative. Traditionally, complex terpenes are synthesized from small and cheap chiral terpenes as starting material in (linear) multistep syntheses [99

• their chaperone-like properties [102][103][104]. Unlike the generation of hydrocarbon backbones in nature, even the biomimetic synthetic construction of terpene scaffolds is usually a multistep process [17]. The second phase of a biomimetic synthesis, in analogy to terpene biosynthesis, involves the

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• in Scheme 1 and detailed synthetic procedures are given below. Briefly, the synthesis of 1 started with the preparation of a BAPTA core via a multistep route adapting the synthetic route developed by Crossley et al. [35]. 1,4-Hydroquinone was benzylated and subsequently nitrated. This intermediate

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• pathways for synthetic transformations that are otherwise quite challenging. Not only the environmental advantages with respect to substituting toxic chemical reagents with mass-free electrons and minimizing the reagent waste generated, but also in terms of shortening of tedious multistep reaction

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• observed in a one-pot synthesis from cyclopentanone, dimethyl fumarate and ammonium acetate. This multistep reaction includes 1,3-dipolar cycloaddition of dimethyl fumarate to the cyclic azomethine ylide formed in situ from cyclopentanone and ammonia. The polycyclic amine product was easily converted into

• nitroxide [4]. Here we report the unexpected formation of a highly strained polycyclic amine from cyclopentanone, dimethyl fumarate and ammonium acetate. This multistep reaction obviously includes the 1,3-dipolar cycloaddition of dimethyl fumarate with cyclic azomethine ylide formed in situ from

Plasma membrane imaging with a fluorescent benzothiadiazole derivative

• Pedro H. P. R. Carvalho,
• Jose R. Correa,
• Karen L. R. Paiva,
• Daniel F. S. Machado,
• Jackson D. Scholten and
• Brenno A. D. Neto

Beilstein J. Org. Chem. 2019, 15, 2644–2654, doi:10.3762/bjoc.15.257

• design and synthesis of small organic fluorescence imaging probes capable of selectively stain plasma membranes has been proven, however, often as a challenging task. The development of small organic probes, in general, has been hindered by the requirement of multistep syntheses to obtain the fluorophore

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• %, respectively (Figure 18). NaN3 is the azidating agent of our choice on efficiency, affordability and availability viewpoint. TBAA can be used as azidating agent instead of NaN3 when anhydrous conditions are required which are useful in multistep syntheses. Azide 7 was successfully synthesised from acetamide 6

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• VUF16216, a compound we have previously communicated as a small-molecule efficacy photoswitch for the peptidergic chemokine GPCR CXCR3. A series of photoswitchable azobenzene ligands was prepared through various synthetic strategies and multistep syntheses. Photochemical and pharmacological properties were

Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses

• Anne-Marie Caminade,
• Artem Zibarov,
• Eduardo Cueto Diaz,
• Aurélien Hameau,
• Maxime Klausen,
• Kathleen Moineau-Chane Ching,
• Jean-Pierre Majoral,
• Jean-Baptiste Verlhac,
• Olivier Mongin and
• Mireille Blanchard-Desce

Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221

• benzaldehyde on the other side. A detailed synthetic process for one of these bifunctionalized fluorophores is illustrated in Scheme 6. It is a multistep process, as 12 steps are needed to get this highly sophisticated fluorophore [58]. In general, the fluorophores are incorporated at the level of the first

Synthesis and properties of sulfur-functionalized triarylmethylium, acridinium and triangulenium dyes

• Marco Santella,
• Eduardo Della Pia,
• Jakob Kryger Sørensen and
• Bo W. Laursen

Beilstein J. Org. Chem. 2019, 15, 2133–2141, doi:10.3762/bjoc.15.210

• even a little lower [41], and does thus not slow down the multistep SNAr reactions. The new ortho-methoxytriarylcarbenium ions with one, two and three para-SEt groups (1–3) are potential precursors for a wide variety of new triangulenium, xanthenium, and acridinium dyes. To elucidate some of these

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

• ][64][67]. The synthesis of the listed organic molecules (Table 3) is generally successful, with high yields in almost all cases. However, some of these synthetic pathways are multistep [124], hence require optimisation for viability and large-scale production. Similarly, pentafulvenes have been used

• as key reactants for the synthesis of natural products and their skeletons (Table 3). The complexity of these molecules requires extensive multistep pathways (ranging from 5–12 steps [127][187]), decreasing overall yields, and thus requiring further optimisation for commercial production. Narayan et

• (3b’ and 6b’) and anti-aromatic (4a’ and 5a’) ring currents. Reaction of 6,6-dimethylpentafulvene with singlet state oxygen to form an enol lactone via the multistep rearrangement proposed by Harada et al. (supporting information was not provided) [51]. Photosensitized oxygenation of 8

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• N-(1-phenylethyl)aziridine-2-methanols 7 Aziridine alcohols 7 are usually prepared by LiAlH4 reduction of the corresponding esters 5 [22][35][36] although a milder method with a NaBH4 and LiCl mixture was also elaborated [37]. A multistep synthesis of (2S,1'R)-7 employing the aziridine ring closure

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

• efficient tools in modern synthetic chemistry, with high atom efficiency, quick and simple implementation, ecofriendliness and a diverse target-oriented synthesis [94]. In addition, both waste production and multistep problems resulting in the expenditure of human labor are significantly reduced. MCRs have

• -phenylimidazo[1,2-a]pyridines (Table 2). Before their work, only three reports of such a formylation have been reported in the literature which suffered from certain drawbacks like difficult to prepare starting materials, multistep reaction, high temperature and the use of expensive catalyst [125][126][127

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

• antitumor, antifungal, anthelmintic, anticancer activities, etc. [5][6][7]. Although a few syntheses of these molecules have been reported in the literature, these generally consist of multistep protocols and require harsh acidic catalysts [5][8][9][10][11][12]. Moreover, only in a very few cases, the

Reaction of oxiranes with cyclodextrins under high-energy ball-milling conditions

• László Jicsinszky,
• Federica Calsolaro,
• Katia Martina,
• Fabio Bucciol,
• Maela Manzoli and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2019, 15, 1448–1459, doi:10.3762/bjoc.15.145

• substitution range of the worked-up products. It is in agreement with previous findings [7]. The synthesis of high DS HP-γ-CD in solution is a multistep process used to minimise reagent loss and the formation of oligo-PGs during synthesis. The high DS and the oligo-PG side chain do not permit acetone

Selenophene-containing heterotriacenes by a C–Se coupling/cyclization reaction

• Pierre-Olivier Schwartz,
• Sebastian Förtsch,
• Astrid Vogt,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2019, 15, 1379–1393, doi:10.3762/bjoc.15.138

• -Wolff-Straße 13, 29699 Bomlitz, Germany 10.3762/bjoc.15.138 Abstract A new novel family of tricyclic sulfur and/or selenium-containing heterotriacenes 2–4 with an increasing number of selenium (Se) atoms is presented. The heterotriacene derivatives were synthesized in multistep synthetic routes and the

• preparation, efficient multistep synthesis routes with good overall yields based on recently published transition metal-catalyzed C–S and C–Se coupling/cyclization reactions in the crucial cyclization steps of iodinated bithiophene and biselenophene precursors. Heterotriacenes 1–4 turned out to be stable and

Easy, efficient and versatile one-pot synthesis of Janus-type-substituted fullerenols

• Marius Kunkel and
• Sebastian Polarz

Beilstein J. Org. Chem. 2019, 15, 901–905, doi:10.3762/bjoc.15.87

• groups on one hemisphere and 5 alkyl chains on the other was reported. The synthesis of this species was elaborate and tedious with relatively low yield, we also failed to introduce more complex substituents than alkyl chains, for instance. The success of the used, multistep synthetic pathway drastically

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• liberation of undesired byproducts [34][35]. In literature, classical small organic molecules’ synthesis has been well explored which includes multistep synthesis [36][37][38][39]. However, the concept of supramolecular chemistry under mechano-milling conditions only has limited number of examples [40][41

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• and luminophores in organic light emitting diodes [26][27]. The synthesis of pyrazolopyridines has been reported in several different multistep manners [28][29][30][31][32][33][34][35][36]. However, some of the reported methods have several limitations such as long reaction time, low yields, boring