Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

•  1, entries 9–11), while the yield raised up to 68% when 0.5 equivalents of base were used (Table 1, entry 12). Finally, in order to shed light on the reaction mechanism (see below), three control experiments were carried out. Under anhydrous conditions (Table 1, entry 13), conversion of the starting

• products, besides relying on performed control experiments, we also refer to the underdeveloped umpolung reactions of imines, considering, in particular, the copper-catalyzed process reported quite recently by Zhang, Hou and co-workers [29]. In our case, we presume the possible reaction mechanism shown in

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• control the size of nanoparticles and the catalyst was stable at room temperature. Higher stability and an easy recovery of the catalyst are the advantages of using graphene as the support. The model reaction was done between phenylacetylene and iodobenzene to evaluate the catalytic properties of the

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• cheap and simple acid enables a temporary protonation while time-controlled decarboxylation liberates volatile CO2 and chloroform as single waste (Scheme 2a). This strategy has been applied with success by the groups of Takata, Leigh, Kim and ours to time control different molecular switches ranging

• generated can be separated from the impurities. Closely related to out of equilibrium systems applied in molecular switches and motors under temporal control, from the amine salt, isolation of the pure free amine occurs through a simple decarboxylation of TCA, releasing volatile CO2 and CHCl3. As a result

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• using a silver-BINAP catalyst combination [25]. Later, the same group could successfully tune the catalytic system to control the regioselectivity in the addition of metal enolate to nitrosoarenes to achieve an α-hydroxyamination [26]. Since then, several groups have shown the use of metal-catalyzed

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• their polarity. Such rigidity posed by the 1,2,3-triazole ring directly bound at C-2 might compromise the most favourable orientations toward crucial interactions of the substituents in the active site. Therefore, this approach was not as promising as expected for TcTS. Regarding the positive control

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• supernatants (50 µL) was then reacted with 100 µL Griess reagent (Sigma Chemical Co., USA). The absorbance was measured at 570 nm using Synergy TMHT Microplate Reader (BioTek Instruments Inc., USA). In the study, L-NMMA (Sigma Chemical Co., USA) was used as a positive control. In the remaining medium, an MTT

• assay was carried out to determine whether the suppressive effect was related to cell viability. The inhibitory rate of NO production = (NO level of blank control – NO level of test samples)/NO level of blank control. The percentage of NO production was evaluated by measuring the amount of nitrite

• 595 nm was measured by a microplate reader, and the medium blank control was set in the experiment. Determination of absolute configurations of sugar units of 1 Compound 1 (2 mg) was hydrolyzed with 1 N HCl (2 mL) at 90 °C for 2 h. The residue was partitioned between EtOAc and H2O to give the aglycone

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• , calix[4]- [9][10][11][12][13] and resorcin[4]arene [14][15][16][17] are the most exploited cavitands due to their inherent limited flexibility and already proved their ability to control the catalytic activity of late-transition metals and particularly gold(I) catalysts [18][19][20][21][22][23][24][25

• devised a new family of triphosphine calix[6]arene gold(I) complexes (Figure 1c) [30]. These cavitands are able to form (pseudo)rotaxane species, by threading viologen-based guests, with a conformational control operated by the sulfonamido hydrogen-bonding donor domain [31][32]. Furthermore, their

• gold(I) nuclei to the opposite sides of the macrocycle, offering them the possibility to approach the cavity, thus exerting any control over the catalytic manifold (Figure 1d). Results and Discussion Synthesis and characterization The synthesis of novel macrocyclic calix[6]arene ligands was first

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• the removal of (as chloride ion), a chlorine attached to a carbon. Robertson and co-workers devised a system for a very accurate determination of rates of reaction by following changes in conductivity, with very precise temperature control. In this way, it was possible to observe systematic deviations

• sufficient for both kH2O/kD2O and kMeOH/kMeOD ratios to be attainable in the temperature range of 15–45 °C (Table 3). Since the solvent isotope effects are quite small, ratios not far removed from unity in almost all cases, precise temperature control has to be coupled with a similarly precise method for

Chemoselective N-acylation of indoles using thioesters as acyl source

• Tianri Du,
• Xiangmu Wei,
• Honghong Xu,
• Xin Zhang,
• Ruiru Fang,
• Zheng Yuan,
• Zhi Liang and
• Yahui Li

Beilstein J. Org. Chem. 2022, 18, 89–94, doi:10.3762/bjoc.18.9

• , Scheme 3). The results indicate that this N-acylation reaction of indole has great potential in practical synthesis. Some control experiments were conducted to explore the reaction mechanism of this transformation (Scheme 4). When S-methyl decanethioate (2i) was adopted without Cs2CO3, no decomposition

• acid (4) (Scheme 4, reaction 4). A plausible reaction mechanism has been proposed based on the results of the control experiments. As shown in Scheme 5, the reaction starts with a base-promoted deprotonation of indole forming intermediate A. In the next step nucleophilic substitution between

• thioesters and indoles. Reaction conditions: 1 (0.2 mmol, 1.0 equiv), 2 (0.6 mmol, 3.0 equiv), Cs2CO3 (0.6 mmol, 3.0 equiv), xylene (2.0 mL), 140 °C, 12 h. Isolated yields are shown. Gram-scale experiment. Control experiments. Proposed mechanism. Optimization of the reaction conditionsa. Supporting

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• signal. Danielson [48] found some errors in Folin’s analytical method and optimized it for better amino acid determination. Martin and Fieser [49] described an optimized method, analogous to Folin’s procedures, with temperature control, producing β-NQSNH4 16 and β-NQSK 20 in high yields (Scheme 2). It is

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• (Δδ = −0.29 ppm, J = 19.6 Hz) as a result of 1JC,D couplings (see Figure S24B and S24C in Supporting Information File 1), again in full agreement with the mechanism by Akhila et al. [10]. A control experiment with (13-13C)FPP, enzymatically prepared from (9-13C)GPP [26], and IPP with FPPS, resulted in

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• control. We also investigated the potency of erlotinib hydrochloride, gefitinib, and verubulin against T98G cells, which were the most sensitive to the novel 4-anilinoquinazolines (Figure S2 in Supporting Information File 1). Compared to the reference drug, doxorubicin, derivative 10b showed promising

• inhibition upon exposure to 4-anilinoquinazolines and compounds with the same scaffolds (erlotinib, gefitinib, and verubulin), and to positive control doxorubicin (MTT assay after treatment for 72 h). Supporting Information Supporting Information File 282: Experimental procedures, characterization data

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• Haopei Wang Zachary T. Ball Department of Chemistry, Rice University, Houston TX, USA 10.3762/bjoc.17.202 Abstract Photo-responsive modifications and photo-uncaging concepts are useful for spatiotemporal control of peptides structure and function. While side chain photo-responsive modifications

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• Entrepreneurship Program (Grant No. 2019CXXL077); Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology (Grant No. OHIC2020Y06).

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• electronic properties of the alkenes to control the chronology of the additions. The rate of addition of the acyl radical to an electro-deficient alkene is about three times greater than that of a styrene derivative [109][110]. The electrophilic radical, adjacent to an EWG, will favor the subsequent addition

• products in diminished yields. This transformation was sensitive to steric hindrance, as ortho-substituted aryl species and bulky alkyl carbazates failed to react under these reaction conditions. Based on control experiments, the authors proposed a tentative catalytic cycle. Initially, in the presence of

• alkenes 175 (Scheme 38) [145]. Control experiments determined the reaction involved a radical process. The proposed mechanism comprised a conventional generation of the alkyl radical through a SET which subsequently adds across the alkene. Compared to Guo’s and Li’s seminal reports (Scheme 19), the

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• ZnI2 reached 94% (Table 1, entry 3), and the reaction with Cu2(OAc)2 as a catalyst did not proceed smoothly (Table 1, entry 1). Other bases such as CH3ONa or t-BuONa (Table 1, entries 4 and 5) were then investigated and no better result was found. In the follow-up control experiments, we studied the

• acids via a triphenylphosphine-mediated deoxygenation process, followed by reaction with sulfonylated diarylmethane 3b to obtain diarylmethane ketone derivatives 6 and 7 [53]. To gain mechanistic insight into this C–S-bond cleavage sulfonylation reaction, some control experiments were conducted (Scheme

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• then, 250–0.12 μg/mL final concentration ranges of the compounds were obtained. In each anti-TB activity determination, a sterility control (without H37Rv working solution) and a growth control (containing no antibiotics) were included in each plate. Effects of DMSO were controlled by inoculated broth

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• [3,4-d][1,2,3]triazines and their derivatives, for example, were reported to function as anticancer compounds [28][29][32], herbicides [19][20][21], antimicrobials [18], and pest control agents [35]. Several possibilities have been reported to gain the scaffold of pyrazolo[3,4-d][1,2,3]triazines

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• acids are widely used in stereoselective oxidative/cross-coupling of two aryl counterparts, asymmetric control of aromatic ring formation, atroposelective functionalization of biaryl compounds, and so on [17][29][30]. In this context, Akiyama (2004) described that chiral phosphoric acids (CPAs) have

• afforded products 46 in moderate to good yields (50–97%), excellent diastereoselectivities (>95:5 dr), and high enantioselectivities (91:9 to 98:2 er, Scheme 15). The control experiments showed that the N–H group in naphthylindoles, the OH group in phenol, and the carboxylate group in azodicarboxylate play

• ) from the reaction of 71 and diethyl ketomalonate (72) under remote control of CPA 19 as chiral phosphoric acid catalyst (Scheme 24). The hydrogen bonding between the ketomalonate and CPA 19 proved to be the most important interaction in the formation of the chiral pocket for the induction of chirality

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• control) gave the desired racemic N-ethoxycarbonyl-1-benzyltetrahydroisoquinolines 5a–h with intact ethoxycarbonyl protection of the phenolic groups (Table 2). Simultaneous phenol deprotection and reduction of the carbamate group (route A) to an N-methyl group was accomplished by lithium alanate reduction

• the alkaloids exhibited the efficiency to activate TPC2 (data not shown). To evaluate the inhibitory potency, afterwards the same cells were stimulated with the TPC2 activators TPC2-A1-P (30 µM) and TPC2-A1-N (10 µM). Compared with the respective solvent control (DMSO), only rac-norcinnamolaurine (3b

• population indicates inhibition of P-glycoprotein. However, none of the tested compounds was able to retain calcein, indicating no P-glycoprotein inhibition. Tetrandrine served as positive control (Figure 5C). In line with that, none of the compounds restored sensitivity of VCR-R CEM cells to the P

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• nuclear Overhauser effect (NOE) NMR spectroscopy are useful tools to monitor and control the chirality when utilizing a modified 1,3-oxathiolane intermediate 65 obtained via enzyme-catalyzed selective hydrolysis. Hu et al. [61] established a green catalyst, STS, for the asymmetric synthesis of lamivudine

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• contrast, only very few reports deal with the oxidative cyclization of nitrogen-containing biaryl intermediates. Ravi Kumar and Satyanarayana mentioned two successful control reactions using 2-phenylbenzylamine and 2-iminomethylbiphenyl with 5 mol % Pd(OAc)2 and 2 equivalents Ag2O in acetic acid at 140 °C

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• -unsaturated carbonyl compounds catalyzed by bifunctional squaramide catalysts has been developed. This methodology offers both enantiomers of β-silyl nitroalkanes in good to excellent yields (up to 92%) and enantioselectivities (up to 97.5% ee) under solvent-free conditions at room temperature. Control

Adjusting the length of supramolecular polymer bottlebrushes by top-down approaches

• Tobias Klein,
• Franka V. Gruschwitz,
• Maren T. Kuchenbrod,
• Ivo Nischang,
• Stephanie Hoeppener and
• Johannes C. Brendel

Beilstein J. Org. Chem. 2021, 17, 2621–2628, doi:10.3762/bjoc.17.175

• benzenetrispeptide (BTP) motifs [18][19][20]. The resulting amphiphilic character of the materials facilitated a control of the kinetic assembly, which provided access to stable nanostructures on a broad length range (<100 nm–2 µm). While the process enables a good adjustment of the length, it relies on a precise

• control of the assembly pathway and requires the use of organic solvents, such as THF and DMF, which limits the applicability in pharmaceutical formulations [21]. For an application in nanomedicine, a length in the range of 100–200 nm is particularly attractive to ensure cellular uptake and to access the

• known size window for a potential enhanced permeability and retention effect (EPR) [22][23]. As an alternative for the assembly pathway control, we opted to apply easy-to-use top-down approaches to tune the length distribution in a straightforward fashion over the above-mentioned length range of

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• [52] was used with commercial nonselective antitumor agent doxorubicin (DOX) as control [53]. The results of antiproliferative in vitro analysis of all tested compounds are shown in Table 4. Among all tested compounds, ketone 3 showed the lowest IC50 value (1.06 μM) towards MDA-MB-231 cells, with