All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• fragmentation to afford alkene 72 in 61% yield. Marcfortine B (8) was synthesized from alkene 72 in seven steps. The enantioselective synthesis of marcfortine C (9) commenced with a catalytic asymmetric cyano-substituted TMM cycloaddition of oxindole 73 and TMM donor 75 with Pd(dba)2/74 as catalyst to give a

• complex B (Scheme 11B). A facile migration–fragmentation process of complex B eliminates a ketone through fragmentation and produces metal-carbene intermediate C. The freshly prepared metal-carbene C is equilibrated to stabilized 1,3-dipole D. D undergoes a diastereoselective [3 + 2] cycloaddition to give

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• frequencies between 20 and 100 kHz were reported in the literature as optimal to enhance the nucleation and fragmentation rates, but the exact optimal frequency is probably reactor and system specific [8]. The exciting properties of the heterocyclic phenothiazine core displaying tunable chemical, redox

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• investigation of the electron impact mass spectrometry (EIMS) fragmentation reactions of these sesterterpene hydrocarbons. Keywords: isotopes; mass spectrometry; reaction mechanisms; sesterterpenes; Streptomyces mobaraensis; Introduction The sestermobaraenes A–F (1–6) and sestermobaraol (7) are a series of

• reaction proceeds in reverse order of a thermal reaction promoted by the thermal conditions of the gaschromatographic analysis) [14]. The fragmentation reactions of structurally simple compounds such as fatty acid methyl esters have been well investigated by isotopic labelling experiments [15][16] and the

• complicated cases, as was exemplified for the side products of bacterial 2-methylisoborneol synthases [22], but in general the structural complexity of terpenes does not allow for such approaches. Nevertheless, more knowledge about the MS fragmentation reactions of terpenes is desirable, but represents a

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• explained by the different stabilization of the respective ions (Figure 3). The abundance of m/z 68 is higher in isoprenyl esters due to the more stable allyl radical cation (Figure 3A). In contrast, prenyl ester fragmentation produces a stabilized allyl cation m/z 69 (Figure 3B), while isoprenyl esters

• 68 (A), m/z 69 (B), and m/z 280 (C). Mass spectra and fragmentation of A: isoprenyl (3-methyl-3-butenyl) 9-octadenoate (9) and B: prenyl (3-methyl-2-butenyl) 9-octadecenoate (10). Red arrows show characteristics in the mass spectra differentiating prenyl and isoprenyl esters. Mass spectra and

• fragmentation of A: isoprenyl 3-acetoxyoctadecanoate (11); B: isoprenyl (Z)-3-acetoxy-13-octadecenoate (12). Separation of the enantiomers of methyl (Z)-3-hydroxy-13-octadecenoate (25) on a β-6-TBDMS hydrodex gas chromatographic phase. A) Natural extract; B) synthetic rac-25; C) synthetic (R)-25; X: methyl 3

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• used to counteract the need for complementary analytic techniques. One of the examples of this is tandem mass spectrometry, where the glycan fragmentation is controlled to obtain the identification of the glycosylation sites and a complete description of the glycan structure compositions, including

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• tool has been particularly upgraded for MS spectrum annotation by adding an intuitive interface with additional features. The upgraded version can depict bond fragmentation, repeating structural unit anomeric groups, adduct ions, different types of glycosidic linkages etc. These advanced features make

• different fragmentation modes [54]. Glycano. Glycano (available at http://glycano.cs.uct.ac.za) is a software tool for drawing glycans. This tool is based on JavaScript, which can be used without the requirement of any server or browser dependency. The interactive interface allows sketching via the drag-and

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• ][119][120][121][122]. There are many approaches to photosensitized fluorination that do not involve direct C–H activation, which are reviewed elsewhere [123][124][125], such as C–C bond fragmentation/C–F bond formation [126], aminofluorination of cyclopropanes [127] and decarboxylative fluorination

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• to identify and measure with GlypNirO. Because there are often multiple potential sites of O-glycosylation within a tryptic peptide and site-specific assignment is challenging with CID or HCD fragmentation information, we used peptide-centric analysis of the plasma O-glycoproteome. Comparing peptide

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• product, with only a complex mixture, as identified by 1H NMR, being isolated. Significantly, in the 1H NMR spectra of this complex mixture we observed complete fragmentation of the sulfonamide unit. Two chiral allenamides (24 and 25) were exposed to the photoredox conditions with 2,4-dimethylaniline, and

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• of 45 °C. MS data were acquired over a range from 100–3000 m/z in positive mode. Auto MS/MS fragmentation was achieved with rising collision energy (35–50 keV over a gradient from 500–2000 m/z) with a frequency of 4 Hz for all ions over a threshold of 100. UHPLC started with 90% H2O containing 0.1

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• , cyclopentanone, and three carbon ring-expanded 1,3-diones from vinyl spiro epoxides [14]. The reaction is initiated by the addition of a thiyl radical to the vinyl epoxide 24, followed by the epoxide fragmentation to the alkoxy radical 25. Then, the β-cleavage to form the carbon-centered radical 26, the final

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• nitroimine (10, 20%), and pivalonitrile (11, 4%) [45]. The proposed scheme for the decomposition of di-tert-butyliminoxyl radical (8) is presented in Scheme 3 [35][45]. It includes formation of C–O dimer 4f followed by the fragmentation to iminyl radical 12, ketone 9, and nitric oxide. The formation of

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• reducible moiety, such as a redox-active ester (RAE). These species can accept one electron from the photocatalyst, and the ensuing reduced species releases the corresponding C(sp3) radical after a fragmentation and CO2 loss. This approach represents an alternative to oxidative decarboxylations, allowing

• exploited as an organic photocatalyst to trigger the reductive fragmentation of phthalimide-based redox-active esters [47]. Other oxidative fragmentations In addition to the decarboxylation reactions, organic photoredox catalysis can be exploited to access C(sp3) radicals via the oxidative fragmentation of

• after the fragmentation of the oxidized form. Due to their attitude towards SET oxidations, these substrates are valuable alkyl radical precursors; however, they are generally less available than carboxylic acids, and the fragmentations release stoichiometric amounts of byproducts. The organic dye

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• fabclavine derivatives, high-resolution MALDI–MS measurements to determine the exact mass and MALDI–MS2 fragmentation patterns of selected derivatives were acquired. If necessary, the measurements were repeated from mutants cultivated in 13C media in order to determine the number of carbons in the sum

• polyamine part, and 795 Da for the NRPS-PKS part (Figure S32, Supporting Information File 1). Considering the fragmentation pattern for compound 31 and standard deviations below 1.3 ppm for further fabclavine derivatives, X. innexi could indeed be confirmed as a producer of fabclavines similar to those from

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• polymerization (NMP) processes, reversible addition-fragmentation chain transfer (RAFT) and atom transfer radical polymerization (ATRP) [118]. While there has been no report available with NIR-sensitized NMP, there exist a few reports for RAFT polymerization with NIR light [119][120][121]. Recently, ATRP with Cu

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• bond by electron transfer into the C–Cl antibonding orbital (Scheme 4A), the same intermediate can be formed by fragmentation of an α-haloketyl radical (Scheme 4B). The acidic environment could lead to easier formation of this ketyl radical. Intuitively, pathway B seems most probable. The reaction in

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

• an intermediate radical anion 40 via SET. Then, the intermediate 40 yields the acylated radical 41 by fragmentation, which, upon intramolecular addition, followed by one-electron oxidation and deprotonation, gives the desired product 37. C–H thiolation Synthesis of benzothiazoles via aerobic C–H

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• , followed by the fragmentation process to give an unusual α-imino silver carbene species D. The intermediate D should be able to isomerize to D’ by conformation rotation to facilitate the addition of activated methene to Ag-carbene, thus forming a new silver species E with a 5-membered ring. The leaving of

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• observation of a fragmentation pattern that does not coincide with the one found in linear peptides, where we would observe the loss of the ʟ-Cys residue. In addition to the sequential loss of ammonia (17 amu) and CO (28 amu) to yield the iminium [M − NH3 − CO]+ (Schemes S4–S11, Supporting Information File 1

• ), as expected for the C-terminal carboxamide, we observed three ions derived from the breaking of two amide bonds, starting from the opening of the macrocycle by the loss of one, two or three amino acid residues as neutral fragments. This fragmentation pattern agrees with the one expected for cyclic

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• with DAPI staining revealed a significant increase in nucleosomal fragmentation and nuclear condensation in 11b treated cells with increasing doses (Figure 6 upper panel) [39]. Furthermore, a cellular functional assay by JC-1 probe, a voltage sensitive fluorescent cationic dye, exhibits membrane

• (Figure 6 middle panel). One of the later steps in apoptosis is ultimately the DNA fragmentation, a process which results from the endonuclease activation during apoptosis. Hence, we further characterized the apoptotic phenomena in HeLa cells by the formation of comet tails (Figure 6, lower panel) and DNA

Anion-driven encapsulation of cationic guests inside pyridine[4]arene dimers

• Anniina Kiesilä,
• Jani O. Moilanen,
• Anneli Kruve,
• Christoph A. Schalley,
• Perdita Barran and
• Elina Kalenius

Beilstein J. Org. Chem. 2019, 15, 2486–2492, doi:10.3762/bjoc.15.241

• complementary information, the ternary complex ions [12 + Me4N + 2A]− (A = PF6−, BF4−, I−) were further investigated by infrared multiphoton dissociation (IRMPD). IRMPD is an MS/MS technique, which can be utilized to study the fragmentation of supramolecular complexes [23]. In these experiments, the [12 + Me4N

Characterization of two new degradation products of atorvastatin calcium formed upon treatment with strong acids

• Jürgen Krauß,
• Monika Klimt,
• Markus Luber,
• Peter Mayer and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2085–2091, doi:10.3762/bjoc.15.206

• NMR spectroscopy, HRMS data and X-ray crystal structure analysis. Keywords: atorvastatin; crystal structure; cyclization; degradation products; fragmentation; stress test; Introduction Over the past decades, the general trend toward globalization of the supply chains for active pharmaceutical

• ). A comparable fragmentation has been observed in the CID (collision-induced dissociation) mass spectrum of atorvastatin, where the base peak observed at m/z 440 clearly corresponds to a loss of phenyl isocyanate [22]. In contrast, refluxing 2 with concentrated aqueous hydrochloric acid (37%) led to

• product 7. Proposed mechanism for the formation of bridged product 6 under cyclization, isopropyl migration and carboxanilide fragmentation. Acidic stress conditions and decomposition products formed. Supporting Information Supporting Information File 251: Materials and methods; stress tests and

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• involved. While the order of oxidative steps in withanolide biosynthesis is still completely elusive [29], we propose that this fragmentation occurs at a late stage, when most typical withanolide functionalisations have already been introduced. Indeed, irinan A (2), irinan B (3) and cinedione (8) can be

• directly linked to the known withanolides 4ß-hydroxywithanolide E (1), withanolide F (5) and withanolide S [23], respectively (Figure S20, Supporting Information File 1). If the fragmentation occurred early in the biosynthesis, this would imply that several biosynthetic enzymes have to tolerate substrates

• -oxidative Grob fragmentation could make use of a push–pull mechanism between C-17 and C-22, building on acid–base catalysis. Alternatively, an enzyme could cleave the C17–C20 diol oxidatively. Several P450 enzymes have been reported to be capable of cleaving diols, presumably via a ferric peroxo

Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

• Jason Yin Hei Man and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2019, 15, 1829–1837, doi:10.3762/bjoc.15.177

• Information File 1). In the MS/MS spectra, fragments corresponding to the loss of the γ-CD and the anthracene stoppers were observed, suggesting the breaking of the glycosidic bonds of the γ-CD and the anthracene–CH2(NRH2)+ bond as the major fragmentation pathways (Figures S24–S27 in Supporting Information

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• CO to give an acyl radical C [35], which then adds to electron-deficient sulfonyl oxime ether 3a to afford 5a. The resulting radical D then undergoes β-fragmentation providing 5a along with the phenylsulfonyl radical E. SH2 reaction between radical E and hexabutylditin regenerates the tributyltin