Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• for tryptophan metabolism in the human body. Thus, the inhibition of these enzymes may help in tumor immunotherapy [105][106][107]. Xu recently found indole-2-carboxylic acid derivatives as IDO1/TDO dual inhibitors. In their effort to synthesize the following bis(indol-4-yl)amine derivatives via a

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• . Another advantage inherent to this class of reagents is their easy purification by a classical acid/base work-up thanks to the presence of the carboxylic acid moiety, even if they could also be purified by standard chromatography on silica gel. They have thus been used in a variety of reactions, the most

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

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• addition of cyclic 1,3‐dicarbonyl compounds, including 4-hydroxycoumarins 1, to α,β‐unsaturated enones 2 (Scheme 1). This versatile Michael reaction afforded (S)-warfarin (3a) and other Michael adducts 3 in high yields and good enantiomeric excess (ee), using (4S,5S)-4,5-diphenylimidazolidine-2-carboxylic

• acid (4) as catalyst [30]. Based on this pioneer work, our research group described an efficient, highly stereoselective, one-pot process comprising an organocatalytic conjugate addition of dimedone or 4-hydroxycoumarin 1 to α,β-unsaturated aldehydes 2 followed by an intramolecular isocyanide-based

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

• target lactone in 61% yield over two steps. The final steps involved a one-pot ozonolysis with quenching under Pinnick oxidation conditions to afford the carboxylic acid derivative in 83% yield, followed by White’s selective C–H oxidation (Scheme 26B). White’s selective C–H oxidation was also applied in

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• , tetrazole (Figure 1b). As an established bioisostere for a carboxylic acid, tetrazole has found significant application within medicinal chemistry [12]. The aromatic tetrazole ring is considered a non-classical bioisostere, differing in size and number of atoms to the carboxylic acid. The functional group

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• terms of overall redox transformation, the reaction formally “hydrolyses” a ketone into a hydrocarbon and a carboxylic acid, and the mechanism remained a black box for over a century, being eventually clarified only in 2007 by a team of British and Russian chemists [8]. One important starting

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

• acrylic monomers possessing different functional groups were explicitly confirmed via FTIR (Figure 4). Regarding the polyacrylic acid-based system (PAA), the broadened signal from 2730 cm−1 to 3703 cm−1 and sharp signal at 3303 cm−1 corresponds to O–H stretching of the carboxylic acid group. The peak

• appearing at 1723 cm−1 can be attributed to asymmetric C=O group stretching vibrations of carboxylic acid groups on PAA chains. The polyacrylamide-based (PAAM) pore substructure spectrum is exhibiting the typical –NH stretching vibrations at 3420 cm−1 and the band at 1656 cm−1 is corresponding to the strong

• due to amine groups' protonation on the polymer backbone via electrostatic attraction, and it responded to monovalent electrolyte with a higher ESR. With the increased pH, HGCM-PAA eventuated with enhanced ESR results arising from the dissociation of carboxylic acid groups. Swelling in saltwater

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

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• synthesize the nucleoside dimer phosphoramidite with the appropriate amide linkage, which can then be introduced into the strand by solid-phase synthesis. These dimers are synthesized by using an amide coupling reagent to condense a 3'-carboxylic acid nucleoside with a 5'-amine nucleoside, where the

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

• ] tailored a microwave-assisted multicomponent reaction for fast and efficient generation of diastereoselective dibenzo[c,e]azepinones. The protocol utilized substituted 2'-formylbiphenyl-2-carboxylic acid 19, benzylamines 20, and isocyanides 21 in TFE and Na2SO4 as drying agent for the construction of

• -proliferative activity against tumor cell lines leading to the discovery of new lead compounds (Scheme 6). A tentative mechanism in Scheme 7 depicts the formation of iminium ion A from the reaction between 19 and 20 after the intramolecular protonation by carboxylic acid. The A conformer stabilized by

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• )chloromethane via a published protocol for radical chlorination of an acetal due to the presence of vulnerable benzylic methyl groups proximate to the acetal [10]. We then synthesized carboxylic acid 9, from which we anticipated creating an aryloxylchlorofluoromethane (10, X = Cl, Scheme 4) via

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• ), and E (3e) comprising the pyrrolo[2,3-c]quinoline skeleton [25]. As demonstrated in Scheme 1, Curtius rearrangement of carboxylic acid 4 resulted in the formation of isocyanate 5, which, upon electrocyclization furnished pyrrolo[2,3-c]quinoline 6. Intermediate 6 was subsequently transformed into

• prepared from an appropriate carboxylic acid through a Curtius rearrangement reaction (50–98% yield). Treatment of urea derivatives 19a–d with CBr4, PPh3, and Et3N afforded carbodiimides 20a–d in 64–75% yield. Compounds 21a–d were obtained in situ following the removal of the TIPS protecting group in 20a–d

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• derivative B22 which was treated with tetrabutylammonium fluoride (TBAF) in THF to obtain the hydroxy derivative C22. Compound C22 was converted to the sodium salt of A22 by using the procedure described for derivative A1. Analogously, compound A23 was prepared starting from 4-aminothiazole-2-carboxylic acid

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• ). Ugi product 6aaa (first letter – isocyanide code, second letter – amine code, third – carboxylic acid code) was the first to isolate in our trials and its structure was confirmed by X-ray analysis (Figure 3) in addition to mass spectrometry, elemental analysis, 1H and 13C NMR data. Compound 6

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• with a covalently attached fullerene molecule [86]. To this end, adduct 13 was obtained from 4-(tert-butoxycarbonyl)phenyldiazomethane and fullerene. Subsequent acid hydrolysis of the protective ester group quantitatively gave a derivative of carboxylic acid 14, a versatile synthon for the synthesis of

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• enantiospecific synthesis of two artificial glutamate analogs designed based on IKM-159, an antagonist selective to the AMPA-type ionotropic glutamate receptor. The synthesis features the chiral resolution of the carboxylic acid intermediate by the esterification with ʟ-menthol, followed by a configurational

• independently be synthesized from the racemic carboxylic acid intermediate (rac)-7 [6]. For such a chiral resolution, we recently discovered that ʟ-(−)-menthol (8) is of use as a chiral auxiliary in the enantiospecific synthesis of the other analogs 2 and 5 (see Figure 1) [4], and the strategy was found to also

• (rac)-16 (87% yield), followed by alkaline methanolysis (74% yield) [17] and Pinnick oxidation (43% yield) [18][19][20], delivered carboxylic acid (rac)-19. Unfortunately, an attempt to improve the oxidation yield was not fruitful; the oxidation of aldehyde (rac)-18 with TEMPO [21] resulted in a lower

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• an electrophile, the crude product 2a was treated with butyllithium, followed by the reaction with carbon dioxide to afford pyrrole carboxylic acid 6 in a good overall yield (Scheme 5). The trifluoromethyl group on the nitrogen was not affected by these highly basic reaction conditions. The mechanism

• transannulation/carboxylation process was demonstrated for the construction of the functionalized pyrrole 2-carboxylic acid with an N-trifluoromethyl functionality. Thus, this work improves the synthetic access to N-perfluoroalkyl-3,4-disubstituted pyrroles. Selected pyrrole-containing natural products, drugs

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• and cis isomers of 2-hydroxy-2-oxo-3-[(phenoxyacetyl)amino]-1,2-oxaphosphorinane-6-carboxylic acid (16, Figure 3) were prepared and evaluated as inhibitors of the zinc-containing β-lactamase II from B. cereus. However, neither stereoisomer had any significant activity [6]. The phosphonodepsidipeptide

• . Structure of 2-hydroxy-2-oxo-3-[(phenoxyacetyl)amino]-1,2-oxaphosphorinane-6-carboxylic acid (16). Synthesis of α-phosphonodepsidipeptides as inhibitors of leucine aminopeptidase. Synthesis of α-phosphonodepsidipeptide 17 as coupling partner for cyclen-containing phosphonodepsipeptides as inhibitors of

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• this effect is not fully clear. It might be linked to the electrophilicity of the carboxylic acid moiety that experiences an electron-withdrawing effects from the fluorine atom (see the comparison of the acidity in Table 2) [58]. In another study, tRNAPro was preloaded with proline analogues, and a

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• Roche and Genentech researchers have described the first route to this scaffold for their FAK and EGFR mutant programs, respectively [1][2]. Both processes started from the versatile 4-iodo-2-methoxynicotinaldehyde (3). Oxidation to the carboxylic acid followed by chlorodehydration afforded the key

Supramolecular polymers with reversed viscosity/temperature profile for application in motor oils

• Jan-Erik Ostwaldt,
• Christoph Hirschhäuser,
• Stefan K. Maier,
• Carsten Schmuck and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2021, 17, 105–114, doi:10.3762/bjoc.17.11

• acid (GCP) or the aminopyridine carbonyl pyrrole carboxylic acid (ACP). At low temperatures, small cyclic structures are formed. However, at elevated temperatures, a ring–chain transformation leads to the formation of a supramolecular polymer. We demonstrate that this effect is dependent on the

• in polar solvents such as DMSO (Ka > 1010 M−1) and water (Ka > 102 M−1) [26], but it also limits its solubility in nonpolar solvents. Therefore, another BU was also employed in this study, namely the less polar aminopyridine carbonyl pyrrole carboxylic acid (ACP). The ACP motif (Figure 2a) can be

• , 64293 Darmstadt, Germany 10.3762/bjoc.17.11 Abstract We report novel supramolecular polymers, which possess a reversed viscosity/temperature profile. To this end, we developed a series of ditopic monomers featuring two self-complementary binding sites, either the guanidiniocarbonyl pyrrole carboxylic

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

• ). These results are in agreement with our previous investigations related to pH-switchable and ionic strength-responsive dendritic amphiphiles appended with dendritic carboxylic acid functionalities [40][41]. The physiological ionic strength thus efficiently screens the repulsive contribution of the

Control over size, shape, and photonics of self-assembled organic nanocrystals

• Chen Shahar,
• Yaron Tidhar,
• Yunmin Jung,
• Haim Weissman,
• Sidney R. Cohen,
• Ronit Bitton,
• Iddo Pinkas,
• Gilad Haran and
• Boris Rybtchinski

Beilstein J. Org. Chem. 2021, 17, 42–51, doi:10.3762/bjoc.17.5

• ][37][38]. Additionally, the aqueous self-assembly incorporating carboxylic acid groups in the covalent unit design has been shown to result in complex and tunable self-assembly modes [39][40][41][42]. Crystalline self-assembly We have found that the nonclassical crystallization of 1 in neutral aqueous