Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• combining thiazole, selenazole, pyrazole, indazole, and indole moieties with both carboxyl functional groups and cycloaminyl units [27][28][29][30][31]. In recent decades, various methods of constructing 1,2-oxazole ring systems have been developed [1][2][3][4][5][6][7][32]. The two primary pathways to 1,2

• the range of 14.4–14.7 Hz, while the 3JHN values were in the range of 1–3 Hz [42][43]. The coupling constants 13C,15N of a series of 15N-labeled pyrazoles gave 1JCN values of 8–11 Hz, while 2JCN were less than 2 Hz [44]. The 15N-labeled 1,2-thiazole moiety was readily determined by measuring the

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• , was reported as recently as 2018 [55]. More interestingly, conventional heating in acetic acid of an enaminone bearing a phenacylsulfanyl substituent adjacent to nitrogen on the C=C bond produced ethyl pyrrolo[2,1-b]thiazole-5-carboxylates in moderate yield, while the corresponding microwave-assisted

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• modified natural nucleobase that did not quench the fluorescence upon hybridization [148]. Köhler and Seitz introduced thiazole orange (TO, Figure 10), an intercalator dye originally designed for DNA [149], as a forced intercalation (FIT) probe in PNA. Because of rotation around the methine bond connecting

• thiazole and quinoline, TO fluorescence is almost completely quenched in ssPNA, but increases significantly upon hybridization to the complementary DNA [150]. The intercalation of TO in PNA–DNA duplex restricts rotation around the methine bond enforcing planarity of the two TO’s aromatic system, which

• base pairs in dsRNA [153][154]. Replacement of thiazole in TO with another quinoline gives bis-quinoline (BisQ, Figure 10), a red-shifted PNA nucleobase analogous to TO [155]. Although binding of BisQ with all four natural DNA nucleobases has not been explored in detail, BisQ-modified FIT PNAs showed

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• group stretching relying on buried g-CN structure in hydrogel network. The vTA photografting can be revealed via distinctive signals such as the emergent peak at 3081 cm−1, corresponding to C–H aromatic stretchings arising from the thiazole ring, the neck at 1687 cm−1 signifies the C=N vibration band

• , and at last the intensified peak at 1419 cm−1 indicates a C–N stretching of the thiazole ring. Proceeding the examination by UV–vis spectroscopy, overlaid absorption spectra of the samples revealed the photophysical differences as expected, since HG does not consist of photoactive g-CN particles in

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• ) or leads to a complex and inseparable mixture of products (when starting from 2a,b). The addition of a base (e.g., triethylamine, N-methylmorpholine, ammonia) which was originally found to be beneficial [33] for the rearrangement of the kinetically formed thiazole to the desired product now caused a

• desired Eschenmoser coupling reaction (route b). Therefore, the nucleophilicity of the conjugated base of the nitrogen (benzenecarbimidothioate or thioimidate) is exerted towards the oxindole carbonyl to give the thiazole. Moreover, if both benzene rings contain electron-withdrawing groups, enhancing

• either the leaving ability of the oxindole nitrogen (R1: Cl, NO2) or the acidity of the >C=NH2+ group (R2: Cl, CF3) increasing the proportion of the nucleophile >C=NH, then the formation of the thiazole (route a) is further accelerated (Scheme 2). Although the addition of a base generates the required C3

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• , Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium 10.3762/bjoc.16.243 Abstract N-Sulfonyl amidines bearing 1,2,3-triazole, isoxazole, thiazole and pyridine substituents were successfully prepared for the first time by reactions of primary, secondary and tertiary heterocyclic

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• a lower affinity [38]. Along the same line, the influence of the length and substituents of the side chains at the G4-DNA ligands have been assessed for quinolinium [43], indoloquinoline [44][45], phenanthroline [46], phenothiazine [47], and thiazole orange [48] derivatives. In these studies, the

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• ; potassium persulfate; thiazole; vinyl azide; Introduction Vinyl azide is one of the most versatile and potent building blocks explored in the synthesis of several heterocycles [1][2][3][4][5]. It can undergo photolysis or thermolysis to afford highly strained three-membered 2H-azirine, which can act as the

• -azirine, an efficient source of nitrogen, was employed as starting material for the synthesis of oxazole with various coupling partners such as aldehyde, trifluoroacetic acid, etc. [8][45][46][47][48][49][50] (Scheme 1). Thiazole is a common structural motif that is found in a wide variety of naturally

• existing alkaloids and a number of pharmaceutically active compounds [51][52][53]. 2-Aminothiazole has a thiourea-like character with a tendency to modulate promiscuously multiple biological targets. Thiazole derivatives also exhibit a broad spectrum of biological activities including antiviral, antiprion

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• Thiazolopyrimidines, whose molecules includes both thiazole and pyrimidine rings, have a structural analogy with the antipsychotic drugs ritanserin and setoperone (Figure 1) [1][2][3]. To date, a wide spectrum of biological activity of thiazolopyrimidines has been determined: anticancer [4][5], antimicrobial [6][7

• the latter [22][23][24][25][26][27][28]. Herein, we report the synthesis of a new series of phosphonylated thiazolopyrimidines. In our studies, chloroethynylphosphonate was used as the phosphonylating agent, which allowed the formation of a thiazole ring with simultaneous phosphonylation of the latter

• the 1H NMR spectra, the proton of the thiazole ring of both isomers is represented by a doublet signal in the low field region at δH 7.91 (3JHP = 3.2 Hz) and 8.41 ppm (3JHP = 7.5 Hz), whereas the corresponding proton of the uracil ring resonated as a singlet at δH 6.61 and 6.71 ppm, respectively. Note

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• oxazoles (17 examples, up to 87% yield) were difluoromethylated but a variety of other heteroarenes turned out to be suitable such as pyridine, imidazole, benzo[d]thiazole, benzo[b]thiophene, benzo[d]oxazole, thiazole and thiophene derivatives (Scheme 6). Copper-based CF2FG-containing reagents Besides the

Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides

• Sabrina Müller,
• Jannik Paulus,
• Jochen Mattay,
• Heiko Ihmels,
• Veronica I. Dodero and
• Norbert Sewald

Beilstein J. Org. Chem. 2020, 16, 60–70, doi:10.3762/bjoc.16.8

• ligand to examine the propensity of these derivatives to bind to DNA. The known intercalator thiazole orange (TO) was chosen as indicator because it exhibits an intense fluorescence band at 526 nm when bound to DNA, whereas it is only weakly fluorescent in solution. The displacement of TO from its DNA

Thermal stability of N-heterocycle-stabilized iodanes – a systematic investigation

• Andreas Boelke,
• Yulia A. Vlasenko,
• Mekhman S. Yusubov,
• Boris J. Nachtsheim and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2019, 15, 2311–2318, doi:10.3762/bjoc.15.223

• Supporting Information File 1) were observed at remarkable high Tpeak values (193.9–210.1 °C). Following these results, it has been intriguing to analyze the influence of the heteroatom in the heterocyclic moiety on the thermal decomposition process. The change of one nitrogen atom to sulfur as in thiazole

• model reaction, especially N-substituted triazoles 4 and 5. In contrast, the reactivity of triazole 3 is comparable to that of benzoxazoles 13 and 14 as well as pyrazole 7 and indazole 8. In our view thiazole 12 is the best compromise in this regard since it is thermally even more stable than 7 and 8

Click chemistry towards thermally reversible photochromic 4,5-bisthiazolyl-1,2,3-triazoles

• Chenxia Zhang,
• Kaori Morinaka,
• Mahmut Kose,
• Takashi Ubukata and
• Yasushi Yokoyama

Beilstein J. Org. Chem. 2019, 15, 2161–2169, doi:10.3762/bjoc.15.213

• (thiazole) [39], and 10c (imidazole) [40] in non-polar solvents, 1c has a much longer absorption maximum in toluene (Scheme 4, Table 2). It should also be noted that the absorption maximum wavelength is longer when the central ethene moiety is part of the aromatic ring than when it is an isolated ethene in

• AcOEt than in toluene, and the thermal back reaction rate in AcOEt was increased. Conclusion We have synthesized three novel thermally reversible 4,4'-(1-benzyl-1H-1,2,3-triazole-4,5-diyl)bis(5-methyl-2-(4-substituted-phenyl)thiazole)s 1o–3o by Ru(I)-catalysed Huisgen cyclization, which is a type of

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries

• Xiao Xie,
• Michela Zuffo,
• Marie-Paule Teulade-Fichou and
• Anton Granzhan

Beilstein J. Org. Chem. 2019, 15, 1872–1889, doi:10.3762/bjoc.15.183

• , the widely used fluorescent probes, such as thioflavin T (ThT, Φ = 0.25, in the presence of 22AG/K+ conditions) and thiazole orange (TO, Φ = 0.19 in the presence of 22AG/K+ conditions) [92], and approach the brightest G4-DNA probes developed so far, such as trialryimidazole IZCM-7 (Φ = 0.52, in the

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

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• ]thiadiazole [2], and benzo[4,5]imidazo[2,1-b]thiazole [3], as well as due to the simultaneous presence of a biologically active phosphorus function in the molecules. Recently, we have shown that the reaction of chloroethynylphosphonates with 2-aminopyridines proceeds through a 5-endo-dig cyclization to form

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• , but with the tetrahydropyrane ring having α orientation. A mixture of epimers at position 4' was also obtained when using the C-5 epimer of substrate 33. Asif et al. [36] developed another 3CR for the synthesis of steroidal thiazole derivatives. As shown in Scheme 11, cholestanic ketone 7 was reacted

• with a thiosemicarbazide and 2-bromo-1-phenylethan-1-one under microwave irradiation to form the steroid–thiazole hybrid 35 in very good yield. As previously mentioned, due to the poor reactivity of steroidal ketones and their imine derivatives, most MCRs with ketosteroids described in the literature

• with an alkynyl seco-cholestane [34]. Multicomponent synthesis of steroid–thiazole hybrids from a steroidal ketone [36]. Synthesis of cholanic pseudo-peptide derivatives by novel MCRs based on the reactivity of ynamide [37][38]. Synthesis of steroid-fused pyrimidines and pyrimidones using the Biginelli

Microwave-assisted synthesis of N,N-bis(phosphinoylmethyl)amines and N,N,N-tris(phosphinoylmethyl)amines bearing different substituents on the phosphorus atoms

• Erika Bálint,
• Anna Tripolszky,
• László Hegedűs and
• György Keglevich

Beilstein J. Org. Chem. 2019, 15, 469–473, doi:10.3762/bjoc.15.40

• elaborated by us for the synthesis of several (aminomethyl)phosphine oxides [10][11]. As regards α-aminophosphine oxides with different P-substituents, only two different types were reported. Olszewski and co-workers synthesized chiral thiazole-substituted aminophosphine oxides 2 through the Pudovik reaction

• of alkylphenylphosphine oxides and the corresponding aldimine derivatives of thiazole 1 (Scheme 1) [12]. Cherkasov and his group applied the Kabachnik–Fields reaction to synthesize a P-chiral aminophosphine oxide with a 2-pyridyl substituent 3 (Scheme 2) [13]. Bis(aminophosphine oxide) derivatives

• isolated in high yields and fully characterized. Synthesis of chiral thiazole-substituted aminophosphine oxides. Synthesis of a P-chiral aminophosphine oxide containing a 2-pyridyl moiety. Condensation of (octylaminomethyl)dihexylphosphine oxide with paraformaldehyde and di(p-tolyl)phosphine oxide

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• corresponding 1H-pyrrolo[3,2-c]pyridine-2,3-dione 4l. The most possible explanation of this fact is the steric hindrance introduced by the N-phenyl substituent, which obstructs the thiazole ring opening. Conclusion In summary, we have developed a novel approach to 1H-pyrrolo[3,2-c]pyridine-2,3-diones (5

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• precursor in the total synthesis of longicatenamycin A [25]. Syntheses of several modified cephems started from dimethyl (2S,4R)-N-Boc-4-hydroxyglutamate (81) [114]. Protected 4-hydroxyglutamic acids (2S,4S)-66 [75][76] and (2S,4S)-85a [84][85] after installation of the thiazole ring at the C1 terminus were

Oxidative and reductive cyclization in stiff dithienylethenes

• Michael Kleinwächter,
• Ellen Teichmann,
• Lutz Grubert,
• Martin Herder and
• Stefan Hecht

Beilstein J. Org. Chem. 2018, 14, 2812–2821, doi:10.3762/bjoc.14.259

• ][47] as the key intermediate undergoing thermal cyclization or cycloreversion, typically in the context of so-called “ECE” and “EEC” mechanisms, respectively [48]. To contribute to this discussion, nonsymmetrical DAEs bearing two electronically distinct aryl moieties (CF3- and Me-thiazole) [5] or

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• the pqs system and 2-(2-hydroxyphenyl)thiazole-4-carbaldehyde used by the iqs system (Figure 1). Strategies addressing las and rhl have been reviewed elsewhere [5][11], while to date one study on iqs inhibition has been reported [23]. Many drug discovery efforts towards effective pathoblockers have

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• the anti-configuration in all cases. In addition, the option for oxidation to the oxazole or thiazole is always enticing as a way of easily accessing a diverse set of molecules. Immediately akin to the oxazole moiety is the oxadiazole heterocycle, which exhibits similar properties. There are several

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• lipophilicity [53]. These structural analogs comprise of branched N-alkyl- and N-cycloalkylpyrroles to test the conformational flexibility towards DNA binding. Hydrophobic N-terminal amides and substituted thiazole replacing pyrrole were installed in order to impart more lipophilicity. All these compounds were

• A has shown much higher affinity than parent distamycin A (preferential selectivity towards G·C sites) due to the presence of an isopropyl-substituted thiazole ring, which makes the molecule more hydrophobic [54]. Recently, a small set of analogs of thiazotropsin was designed and synthesized to

• nicotinamide as shown in the Figure 4 (conjugate 5). Suckling et al. further demonstrated another structural analog of thiazotropsin conjugate 6, a heterocylic triamide containing thiazole carboxylic acid, which showed significant activity (MIC = 63 nM) against Trypanosoma brucei [55]. However, the authors