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

• , antitumor, and antiviral effects [15]. Mechanistically, they have been shown to block two pore channel 2 (TPC2), an endolysosomal cation channel which is important for cellular migration and survival [6][15][46][47]. In our recent search for TPC2 blockers with antiproliferative potential we identified ring

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

• observations about the preferred migration of the more substituted carbon atom during the Schmidt reaction [49]. Also, a retention of configuration at the C-13 position was confirmed by NOE NMR experiments. The chemical shift of some protons in compounds 13 and 14 exhibited effects of magnetic anisotropy from

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• transferred between the oxygen atoms after the alkyl migration, making it especially useful in synthetic strategies using these protected intermediates. Additionally, the reaction was found to be useful in the kinetic resolution of a racemic mixture of chiral substrates possessing both alkyl and aryl α

• example of the use of conjugation to drive an α-ketol rearrangement. This study elegantly illustrates the synthetic power of α-ketol rearrangements, whose suprafacial migration ensured that the α-ketol moiety present in the target product 31 was installed with correct stereochemistry. Taking inspiration

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• The skin acts as a protective barrier against the environment with immunologic and sensorial functions [7]. As of now, the way of dealing with extensive skin loss would be wound dressing, autografts, and allographs but there is a lot of room for improvement. Cryogels can cause cell migration which

• shows promise to solving these problems and enhancing skin substitutes [7]. An optimal bio-scaffold would have to be biocompatible, biodegradable, have a high pore connectivity and swelling ratio as its function is to promote cell growth and act as a nucleus for cell migration. Moreover, ideally it

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• followed by esterification with 3-butenoic acid (37) under Steglich conditions (Scheme 3). The resulting product 38 was isolated in 86% yield. A subsequent ring-closing metathesis reaction and DBU-assisted double bond migration then furnished the anticipated structure 39. The PMB functionality was removed

• -promoted double bond migration. The cyclopropyl functionality in 46 can be assembled from the reaction of sulfur ylide and the α,β-unsaturated ketone 47, which in turn can be realized from the cross metathesis between commercially available ethyl vinyl ketone (48) and the C2-symmetrical diene-diol 49. The

• all the centers of the stereochemical brevipolides but in the mirror image of the natural configuration. After sequential ring-closing metathesis, base-promoted olefin migration, and MEM removal, the ent-brevipolide H (ent-8) was obtained. This compound showed inhibition activity in the preliminary

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• , whereas the polymers 157 and 158 were containing 25–75 mol % azulene. The photophysical studies carried out on the neutral/protonated polymer series 155 and 158 were supportive of the fact that the optoelectronic property, electronic interactions, and exciton migration can be tuned by varying the density

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• -component reaction in which a cobalt-Cp*-catalyzed C–H bond addition afforded complex scaffolds in good yields (Scheme 37B and C) [193]. The authors explained the stereoselectivity by means of a mechanism involving a hydride migration suffering influence of steric effects related not only to the catalyst

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• the Pd(II) intermediate, with retention of the configuration. When 1d-3,3-d2 was used in the presence of the Pd(II) catalyst, only the isotopomer 2d-6-d1 was obtained, indicating the migration of the Pd(II) alkyl complex from the site of the cyclization C(4) to the α-carbonyl position and pointing to

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• XRD-analysis (Figure 3). It was found that both salt 17a and base 18a can be isomerized into isomer 19 under heating in the presence of AlCl3 via migration of the 3-Ph-group into the position 2 (Scheme 6). Compounds 18a, 19 can be quantitatively N-alkylated by MeI at room temperature and by BnBr at 40

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• to the electrophilic iminic carbon took place in a quite rigid system, with chelation of the Lewis acid with the nitrogen of the imine and carboxylate oxygen, forming a five-membered ring. The migration of the vinyl group occurred to the Re face of the imine, which is less shielded than the Si face

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• and 12 under these conditions produced the expected thioglycosides 18 and 19, respectively. Difluorinated derivative 13 decomposed on reaction with the PhSTMS/ZnI2 system. The separation of the anomers of products 14–19 was attempted because of the risk of thiophenyl migration in the subsequent C6

• (Scheme 3). Reaction of β-thiogalactosides possessing an unprotected C6 hydroxy group with DAST was accompanied by migration of the anomeric thio-aglycone to C6 [41][52] as shown for β-thiogalactoside β-17, which mostly delivered migration product 32 (Scheme 3, see also the synthesis of compound 24 in the

• Supporting Information File 1). However, β-thioglucoside β-14 yielded only 6% of migration product 33 together with the main C6-fluoro product β-22, suggesting that starting fluorinated 2-azido-thioglucosides were significantly less prone to thiophenyl migration than 2-azidothiogalactosides were. This was

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• anion III on the enone intermediate 4 (path A), followed by elimination of OTs affords the corresponding β-triazolylenone 3 (Scheme 4) [52]. The β-O-tosylcyclopentenone intermediate 4b can also undergo intramolecular tosyl migration to form a stable C-tosylated product 4b’ (see also Scheme 3b and c

• intermediate VI (R = Me) and to the axial OTs group in the resulting intermediate VII (R = Me) in the event of equatorial approach of the nucleophile. Therefore, the reaction proceeds in the case of 1,3-cyclohexanedione (2a), but stops at the tosyl/mesyl migration step and does not proceed further in the case

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• pesticide cyhalothrin [106] by the fungus Cunninghamella elegans. In the former, 19F NMR demonstrated the appearance of phase 1 (oxidative) and phase 2 (conjugative) metabolites, and in the latter, it was possible to monitor the migration of the pesticide into the biomass in the first 24 h after its

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• of multivalent interactions is the extracellular adhesion protein L-selectin. L-Selectin plays a critical role in inflammation processes by supporting the migration of leukocytes to inflammatory sites via adhesion to endothelial cells [19][20][21]. On a molecular level, a cationic binding site [22

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

• trimethylsilyl ether. The electron-rich end of complex A attacks the carbon dioxide to give carboxylate B. Migration of the TMS group on carboxylate B generates the 1,3-dipole on C in the form of TMS carboxylate. An intermolecular [3 + 2] cycloaddition of C and alkene D (see Scheme 3B, inset) gives the

• 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

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• core, would be suitable for the C4 deoxyfluorination of intermediates 2–5. However, it is well documented that undesired rearrangement products with 1,2-aglycone migration [26][27][28] or skeletal rearrangements [29] have been observed during fluorodeoxygenation of glycopyranosides with DAST

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• neighboring silicon leads to silyl migration and consequently to an isomeric mixture, which can be separated by column chromatography [30]. However, this procedure does not secure high yields and the careful separation of a sufficient amount of the 2’-O-silyl isomers is rather time consuming. Additionally

• migration of the TBDMS protecting group and consequently formation of the 3’-O-TBDMS isomer under Sonogashira conditions, which accounts for the reduced yield. This certainly can be counteracted by further reducing the reaction temperature of the Sonogashira coupling. Under the conditions applied here

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

• w1•+ to x1•+ (Scheme 2B). The inductive cleavage with hydride migration leads to y1•+ representing the minor fragment ion at m/z = 122 that may efficiently lose two hydrogens to give the conjugated system in z1•+. Fragmentation mechanisms for sestermobaraene B (2) The position-specific mass shift

• rearrangement to a2•+ and a hydride shift to b2•+ (Scheme 3A). This hydride migration is in reverse order compared to a similar step along the cationic cyclisation cascade during the biosynthesis of 2 (Scheme S1 in Supporting Information File 1). The subsequent inductive ring opening to c2•+ and α-cleavage of

• loss of C13 starts from 2•+ by a hydrogen rearrangement to l2•+ and an α-fragmentation to m2•+, followed by another hydrogen transfer to n2•+ and α-cleavage to o2+ (Scheme 4A). The second possibility with the loss of C1 is explainable from l2•+ by a hydrogen migration to p2•+ and an α-fragmentation to

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• formed during the cyclization reaction of 16 compared to phenyl nitrene [42]. Besides H-SN4 13, which is formed by insertion of the nitrene N-atom into the C3–H σ-bond of the thienothiophene in 16 and simultaneous migration of the H-atom to the nitrogen, mostly undefined black oligomeric or polymeric

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• like phenyl or isopropenyl at the bridgehead position were analyzed for the first time in different solvents and upon irradiation with different wavelengths. In all cases, a regioselective photoinduced 1,5-phenyl migration leading to vinyl ketenes from the more congested site of the molecule to the

• photoreactions of bridged bicyclic systems like 3a–g were carried out [9][10][11][12][13]. These molecules contain a δ-keto-α,β-enone system juxtaposed with a (cis)-dibenzoylalkene moiety. Interestingly, photoreactions of 3a–f were found to follow regioselective photoindiuced 1,5-phenyl migration from the more

• -phenyl migration have been found to be subtly dependent on the substitution pattern. For instance, the rate of 1,2-AS in 3b has been found to be much faster than the one of 3e. It is probably due to the extra hindrance of gem-dimethyl substituents at C-7 position in the latter. Moreover, only 1,2-AS

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• explained via the migration of the bromide ion followed by the aromatization of bromodienone compound 71 to the stable o-bromohydroxysumanene 72. Having compound 71 in hand, next it was treated with silver acetate in H2O/THF (1:1) to furnish compound 74. On the other hand, alcoholysis of the same compound

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• -fluoroalkylated indanones are shown in Scheme 5 [28][38]. Thus, the reaction presumably proceeds as follows: (1) transmetalation of the cobalt catalyst with 2-formylphenylboronic acids (2) gives the arylcobalt species Int-1, (2) insertion of the alkyne 1 into the [Co]–Ar bond (see Int-2a) [39], (3) migration

Clustering and curation of electropherograms: an efficient method for analyzing large cohorts of capillary electrophoresis glycomic profiles for bioprocessing operations

• Ian Walsh,
• Matthew S. F. Choo,
• Sim Lyn Chiin,
• Amelia Mak,
• Shi Jie Tay,
• Pauline M. Rudd,
• Yang Yuansheng,
• Andre Choo,
• Ho Ying Swan and
• Terry Nguyen-Khuong

Beilstein J. Org. Chem. 2020, 16, 2087–2099, doi:10.3762/bjoc.16.176

• -throughput analysis [9]. In CE-LIF, released and fluorescently labelled glycans migrate over a capillary and are identified by comparison to the standardized migration time with external or internal oligosaccharide standards. In order to achieve standardized migration time in a high-throughput manner

• , migration time is generally calculated by correlation with internal standards that bracket the time of elution of the glycans of interest [10]. This process is used to calculate a glucose unit (GU) which helps to align the datasets so that the GU of each glycan can be used to identify the glycan through

• databases and software (among others) are discussed in a recent review [15]. A long standing problem associated with the analysis of large sets of electrophoretic data generated during bioprocessing is inevitably the drift of the peak migration time and area under the curve pertaining to glycan structures