Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• carbonyl carbons of seven amides, two carboxylic acids, and one ester. Also present were forty-one sp3-hybridized carbon signals which were assigned to fourteen methines, fifteen methylenes and twelve methyl groups The 1H NMR spectrum exhibited signals at δH 4.19 (ov., 1H, H-2), 4.08 (dd, J = 8.8, 6.0 Hz

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• addition (if X = H) or proton cleavage in the case of X = OH. Amine mediators are also suitable for the generation of radical species from CH-acidic substrates, such as β-dicarbonyl compounds. This reactivity was used in the dehydrogenative annulation of N-allyl amides with β-dicarbonyl compounds with the

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• ultimately found success with the benzamide derivative 5, which could be prepared from the mixture of 4 and its C7-epimer in 93% yield upon treatment with benzoyl chloride. Recrystallization of the resulting mixture of diastereomeric amides from cyclohexane improved the dr from 83:17 to 95:5 (as determined

• , respectively. At this stage, we started to investigate alternative methods to cleave the amide via reduction. Achieving selective C–N-bond cleavage of amides under reductive conditions is still a largely unsolved problem since a C–O-bond cleavage is typically the preferred mode of reactivity, especially when

• using hydride reducing agents [13]. Nevertheless, specialized conditions for achieving C–N-bond cleavage of amides using SmI2 [13], Tf2O/Et3SiH [14], and stoichiometric Schwartz’s reagent [15] have been reported; however, none of these methods was successful in reducing amide 5 to the desired amine 4

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• showed a modest induction (entry 3). Conclusion Exploratory efforts toward new C1-symmetrical CPAs were described. Four CPAs were synthesized and three evaluated. The syntheses are straightforward, inexpensive, and scalable. Resolution via the separation of diastereoisomeric phosphorus amides could be

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• cage nitrogen atoms) and/or rotamers (restricted rotation around amide C–N bonds), which is well-known for amides and carbamates (Figure 4a). The activation barriers for the rotation across amide C–N bonds in 4a and 4c estimated by DFT (18.4 and 19.4 kcal/mol, respectively, ωB97XD/Def2TZVP, gas phase

• ) are close to those observed experimentally for amides and carbamates [42][43]. Upon changing the solvent to CD3OD or D2O the spectra become much simpler and a picture expected for a Cs symmetrical structure is observed (for example, cf. 1H NMR spectra of Bn-4c in different solvents shown in Figure 4b

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• 28 (note the missing methyl group) had been reported to be devoid of antimycobacterial effects at 6.25 µg/mL (30 µM) [162]. Moreover, a screening at GSK identified the amides 29 and 30 [163][164], and amine 25 was also reported but only for an effect on M. tuberculosis glutamine synthetase [165

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• -diketo esters 2 (Scheme 1). On the other hand, two carboxylic acid functionalities adjacent to a keto group result in mesoxalic diesters 3, or mesoxalic ester amides 4. The increased electrophilicity of the keto group and the high density of these complex functional groups make such structures attractive

• , (−)-preussochromone D, (−)-jiadifenoxolane A, palau’amine, jatrophen, (−)-hopeanol, (+)-campthotecin, isoretronecanol, corynoxine, (+)-gracilamine, (−)-irofulven. Mesoxalic diester and ester amides as key intermediates: (+)-awajanomycin, (−)-aplaminal, cladoniamide G. α,β-Diketoesters as key intermediates

• diesters and ester amides as key intermediates (+)-Awajanomycin Diethyl mesoxalate (90a) is a valuable building block due to the high density of carbon atoms in high oxidation states. As a vic-tricarbonyl compound, its central keto group is an especially potent electrophile. The Koert group used this

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• ). N-(1-Naphthyl)formamide (6) was obtained in satisfying yield, while the methyl and tert-butyl ester moieties affected the reaction outcome (Scheme 1, amides 7 and 8). Secondary amines were also tested under the developed conditions; N-methylaniline provided the desired product 9 in 39% yield, while

• using secondary aliphatic amines such as dibenzyl- and methylbenzylamine, which provided amides 16 and 17 in 87% and 74% isolated yields, respectively. Furthermore, the methodology allowed us to synthesize a set of aromatic formanilides (amides 18–20, Scheme 2). Indeed, the deactivated p-nitroaniline

• was successfully converted into the corresponding formamide 19 as was the poorly nucleophilic diphenylamine (Scheme 2, amide 20). Lastly, we aimed to apply the procedure to the acylation of a series of amines. To our delight, we successfully extended the methodology to the mechanosynthesis of amides

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• . Several attempts were made to combine the benzothiazine motif with amino acid methyl esters (Scheme 4) using coupling agents (EDC, COMU, T3P®, etc.) or through acid chloride (SOCl2 and (COCl)2) in a flask with stirring or under ball-milling conditions. However, we were unable to isolate the desired amides

• the amino acids. However, these reactions proved to be unsuccessful due to the high reactivity of the bromo derivative. On the contrary, coupling of the less reactive amides formed from pyruvic acid and the amino acids 16a and 16b was accomplished (Scheme 5a), and several different conditions were

• and amides with amino acids. Benzothiazine derivatives with a carboxylic function in the C-3 position exhibit low stability under acidic as well as basic conditions, which complicates the synthetic utilization. As such, direct coupling of 4H-benzo[b][1,4]thiazine-3-carboxylic acid with amino acids

Electrochemical Friedel–Crafts-type amidomethylation of arenes by a novel electrochemical oxidation system using a quasi-divided cell and trialkylammonium tetrafluoroborate

• Hisanori Senboku,
• Mizuki Hayama and
• Hidetoshi Matsuno

Beilstein J. Org. Chem. 2022, 18, 1040–1046, doi:10.3762/bjoc.18.105

• amidomethylated products in good to high yields. Keywords: electrochemical oxidation; Friedel–Crafts type amidomethylation; N-acyliminium ion; quasi-divided cell; trialkylammonium salt; Introduction Oxidation of amides generates useful intermediates, N-acyliminium ions, which have been widely used in organic

• synthesis [1][2][3][4]. For example, Friedel–Crafts-type amidomethylation [5][6][7][8][9][10][11][12][13][14][15] proceeds efficiently by the reaction of N-acyliminium ions with electron-rich arenes to give the corresponding amidomethylated products in good yields. Since amides are important intermediates

• -acyliminium ions in chemical methods has been generally accomplished by the reaction of amides with chemical oxidants, such as peroxides and persulfates at high temperature (path a in Scheme 1) [10][11][12][13]. A metal catalyst or a photocatalyst consisting of metals, such as ruthenium or iridium, is also

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• tested in the reaction. To our pleasure, both aliphatic and aromatic amides reacted smoothly and provided the expected products in satisfactory yields, with the acetyl groups being unaffected. This suggested that the N-acetyl groups in N-substituted carbonylimidazoles were well tolerated during the

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• alcohols [24], methoxides [23][25][26], carboxylic acids [27], amides [28], ketones [29][30], an exo-olefin [31], and lactones [32]. Elucidating the mechanisms of structural diversification is essential when considering the synthesis of unnatural azoxides by a synthetic biology-based approach. However

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• -supported combinatorial approaches [11][12][13]. The most relevant comparison of peptoids with peptides is in fact with polyprolines due to the presence of backbone tertiary amide linkages, much more prone to cis/trans equilibria than secondary amides. Indeed, in proteins, cis-amide bonds are most often

• through steric and electronic interactions involving peptoid amides and nearby side chains [17][18]. For example, N-substituted monomers bearing benzylic-type Nα-chiral groups including the phenylethyl [19][20][21], naphthylethyl [17][22][23][24], and triazolium groups [25][26][27], alkyl ammonium [28

• ], tert-butyl/α,α-gem-dimethyl [29], or fluorinated groups [30] will preferentially form cis-amides (Figure 1A). Peptoid helicity modulation has also been investigated through specific placement of chiral and achiral monomers [31][32]. Comparatively fewer N-functional monomers capable of promoting trans

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• due to their specific characteristics such as basicity, hydrogen bond forming ability, water solubility, and especially because of pyridine rings are bioisosteres of amines, amides, N-heterocyclic rings and benzene rings [1][2][3][4][5]. A special type of pyridine, the 4-pyridones, is also fairly well

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• diverse electronic distribution between aliphatic and aromatic formamides. Concerning aromatic amides, the presence of electron-withdrawing (EWG) or electron-donating groups (EDG) further affect the tautomeric equilibrium, promoting or weakening the reactivity of the substrates. In this case, the yields

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• acylating reagent (1.0 equiv) in DCM and in the presence of TEA (1.1 equiv). The amides 27 and 28 were obtained with moderate yields (78% for 27 and 65% for 28) – values that are comparable to those previously described for the analogous ethyl derivatives [12][13]. Finally, the base-catalyzed intramolecular

• transesterification (cyclization) led to the desired products 1 and 2. In the case of amides 27 and 28, the reaction conditions for the cyclization were slightly modified, i.e., the reaction time was prolonged to 24 h and the precipitated product was washed with hexane to remove traces of borneol. No changes in the

• de were observed and the presence of the major S-enantiomer in the products 1 and 2 was confirmed by chiral HPLC analysis. Moreover, an enhancement of the abundance of the major epimer in the nitroaldols 22, 24, and 26 as well as the amides 27 and 28 was examined. Generally, epimers represent pairs

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• )pyrroles [15]. The CsF-promoted nucleophilic addition of isocyanides to bromoacetylenes furnished the functionalized bromovinyl amides followed by Pd-catalyzed formation of 5-iminopyrrolone [16]. Sequential nucleophilic addition/intramolecular cyclization of amidine with bromoacetylenes led to imidazoles

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• guest molecule with an inwardly directed carboxylic acid group. The hydrogen bonds provided by a cyclic array of secondary amides around the rim stabilized the vase-like conformation of the complex (Figure 11b). Adding the epoxyalcohol 39 to the solution of I formed 5-membered ring product 40

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• of their derivatives [12][13][14][15][16][17][18][19][20][21][22]. For example (Scheme 1), a one-pot Tf2O-mediated assembly of amides, amines, and ketones provided 3,4-dihydroquinazolines in good yields via successive triflic anhydride-mediated amide dehydration, ketimine addition, and Pictet

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• by a review article devoted to aza-Michael reactions of amines and amides [17]. The evolution of the understanding of noncovalent activation modes led to the realization that anion-binding is a critical feature in many transformations. Halide anions are highly relevant and widely occurring within

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• in this first attempt, LDA was replaced with LHMDS and the reaction was allowed to warm to room temperature overnight (Table 1, entry 2). LHMDS is a weaker base than LDA and should not deprotonate α-substituted amino acid amides [53][54]. No full conversion was observed either and both yield and

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• alcohols [13][14][15] (Scheme 1a); (3) oxidative condensation of aldehydes with vicinal amino alcohols [16] (Scheme 1b); (4) cyclization of N-allylamides in the presence of electrophilic reagents or radical initiators or catalysts [17] (Scheme 1c); (5) direct synthesis from alkenes and amides or nitriles

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• , carboxylic acids, tetrazoles, aldehydes, amidines, and amides [7][8][9][10][11]. This has been suitably transformed into structurally diverse and complex molecules. In 1927, Pongratz reported a method towards cyanation reactions [12]. From then, onwards, cyanation gained prime focus and achieved much

• °C for 24 h (Scheme 13). Differently substituted aromatic amides with a range of functional groups such as fluoro, chloro, bromo, ester etc. were tolerated well in this method. The authors also performed the cyanation of heteroarenes at C-2 and C-3 positions and obtained excellent results. Various

• reactivity was observed for 2° and 3° alkyltrifluoroborates under the optimized conditions. The authors were able to improve the product yield by increasing the amount of TsCN and avoiding the use of additive (Scheme 18). A wide variety of functional groups such as esters, cyano, amides, ethers, ketones

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• very attractive as HAT catalysts as demonstrated by previous works using secondary amides [8][9], sulfonamides [10] and quinuclidine [11][12], the latter being broadly explored in the literature for several functionalizations along with its derivatives [11][12][13][14][15][16][17][18][19][20]. DABCO is

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• /min. Peaks for (S)- and (R)-4' were detected at 11.3 min and 14.3 min, respectively, by monitoring the absorbance at 250 nm. Preparation of PGME amides 6a and 6b In a manner similar to a procedure from [21], to a solution of 6 (1.0 mg, 3.2 μmol) in dry N,N-dimethylformamide (100 μL) and N,N

• products. Chiral phase HPLC analysis of methyl ester 4'. Italicized numbers indicate peak areas. COSY and key HMBC correlations observed for 6. ΔδH(S-R) values in ppm calculated from PGME amides 6a and 6b. Selected examples of the related compounds derived from the strains in the genus Streptomyces (a) and