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

• amine derivatives (e.g., hydrochloride salt, mandelic acid salt, phthalimide, ketopinic acid amide, salicylaldehyde imine, p-toluenesulfonamide, acetamide, etc.), all attempts to separate the resulting isomers (which were oils) were similarly unsuccessful. Seeking an alternative to column chromatography

• anticipated that the amide 5 could be hydrolyzed to give a single enantiomer of amine 4. However, we found that amide 5 was remarkably resistant to hydrolysis, even under forcing conditions. For example, no amide hydrolysis was observed in concentrated aqueous NaOH solution at reflux (with or without an

• , 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

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• , glycogen synthase kinase 3 (GSK-3), leucine-rich repeat kinase 2 (LRRK2), tyrosine phosphorylation-regulated kinase-1A (DYRK1A) and CDC2-like kinase 1 (CLK1), and fatty acid amide hydrolase (FAAH) [4]). Similar properties were ascertained for 1-deazapurine derivatives (imidazo[4,5-b]pyridines) and

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• building blocks 5 and 8 in hand, ketone 9 was prepared via a palladium-catalyzed Sonogashira coupling reaction in a yield of 95%. The precursor 10 for the gold(I)-catalyzed [19][20][21][22][23][24] cycloisomerization was then synthesized by treating ketone 9 with sodium bis(trimethylsilyl)amide (NaHMDS

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

• accomplished easily, either by chromatography over silica gel or crystallization. Subsequent Stec reaction proved to be a reliable method to convert the resolved amide into the chiral thiophosphorus acids. The CPAs synthesized clearly failed to induce any significant asymmetry. It is interesting to note

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

• as synthetic receptors to form host–guest complexes based on H-bond interactions with amide/carbamoyl groups [31][32]. In addition, N-TAADs can be viewed as analogs of hexahydrazide ligands, which were reported to stabilize high-valent metal complexes [33][34]. Since N-amino groups can be easily

• the previously described 3O-TAAD derivatives 2 [21]. In all TAADs, the nitrogen with an equatorial substituent is more deviated (0.55–0.61 Å) from the mean plane created by three carbon atoms of the triazinane ring than the nitrogen atom bearing and axial group (0.37–0.45 Å). 3N-TAADs 4 bearing amide

• and carbamate groups form inclusion complexes with water or methanol (Figure 3a–d). In the crystal state, a common hydrogen-bonded motif is observed, in which the guest molecule is located in a pocket created by amide/carbamate groups and the triazinane ring of the 3N-TAAD structure that is well

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• inhibitors to disrupt bacterial alginate production [3]. We recently disclosed the first series of targeted sugar nucleotide probes for GMD (Figure 1b) [4][5][6]. A C6-methyl analogue 6 was oxidised by GMD with direct evidence for a ketone product obtained. Most recently, C6-amide sugar nucleotide 7 was

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• protocol proceeds in an undivided cell equipped with graphite plate electrodes under constant current conditions. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diketones, can be converted to the corresponding 2-aminothiazoles. Mechanistically

• performed in an undivided cell with NH4I as the mediator and cheap graphite plate as the working electrode. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diones proved to be compatible with the protocol. Since external oxidants and

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

• ]. The α-ketoester 41 was accessible from amide 38, which in turn was obtained from allylic alcohol 37. Oxidation and Horner–Wadsworth–Emmons reaction with phosphonate 39 delivered the silyl enol ether 40, which was deprotected and cyclized via a Grubbs metathesis to α-ketoester 41. Subsequent

• aniline 94 in three steps (Scheme 16). Subsequent deprotection and condensation with dimethyl mesoxalate (90b) gave imidazolidine 95. With compound 95 at hands, five further steps gave (−)-aplaminal (96) in a good overall yield of 19%. Cladoniamide G The unsymmetrical mesoxalic acid amide 102 was used by

• mesoxalic ester amide 102 in a Friedel–Crafts reaction followed by a spontaneous lactamization to give (rac)-cladoniamide G (103). The mesoxalic ester amide 102 was synthesized from malonyl chloride 104 through amidation and Regitz diazotransfer, yielding diazo compound 105. Subsequent oxidation and

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• ball mill (Figure 1c) enhances the depolymerization of acid-impregnated chitin more selectively towards glycosidic bond cleavage (i.e., backbone rupture) over amide bond breakage (i.e., deacetylation) [38][45]. Notably, the result is different for the reaction in solution, where scission of both bonds

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

• ]. In this work, we aimed to set compatible conditions to access formamides, envisioning the possibility of generating the isocyanide in a one-pot, two-step reaction. However, to the best of our knowledge, despite the notable improvement in the mechanochemical synthesis of the amide moiety [44][48][49

• HCO2H derivatives and CH3CO2H and two activating agents for promoting amide coupling. Results and Discussion We started our investigation by reacting p-methoxyaniline (1.0 mmol) with ammonium formate (3.0 mmol) (Table 1, entry 1) in a zirconia jar in the presence of one milling ball of the same material

• 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

• the original convergent synthesis plan. Instead of the classical amide coupling, bromo derivative Int1 should allow the formation of the benzothiazine ring as the final step. As an α-halocarbonyl compound, we tried to prepare Int1 through the coupling of bromopyruvic acid and ester, respectively, with

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• indicated by a strong NOESY correlation between the amide NH and the neighbouring methyl group. The structure of TDD These findings not only challenge the originally assigned structure of (E)-4 [9] and confirm the structural revision of (Z)-4 [1], but also question the suggested structural revision that

• material that was obtained as a viscous oil, failed. The X-ray crystallographic analysis of (rac)-4 showed an interesting dimer interaction of its enantiomers through hydrogen bridges between the amide (NH-CO) groups (Figure 2, for crystallographic parameters cf. Supporting Information File 1, Table S1

Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes

• Mana Kitano,
• Tsuyoshi Saitoh,
• Shigeru Nishiyama,
• Yasuaki Einaga and
• Takashi Yamamoto

Beilstein J. Org. Chem. 2022, 18, 1154–1158, doi:10.3762/bjoc.18.119

• addition, 1H NMR and FTIR spectra for the crude compound did not show characteristic peaks derived from carboxylic acid and amide. In order to clarify the role of the anode material, we carried out electrochemical measurements (Figure 1). Cyclic voltammetry was performed using BDD as a working electrode. A

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

• in organic synthesis and sometimes appear in biologically active compounds, pharmaceuticals, agrochemicals and functional molecules, amidomethylation induced by N-acyliminium ions is a helpful and valuable protocol for direct introduction of an amide function into organic molecules. Generation of N

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• produced a bridged cyclic 2-oxabicyclo[2.2.1]hept-5-ene D. The further hydration of intermediate D gave intermediate E, which was in turn transferred to cyclopentenyl intermediate F by the ring opening of the bridge ring. In the cyclopentenyl intermediate F, the hydroxy group and the amide group clearly

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• . Moreover, since no detectable transformations took place when quenching the reaction at −78 °C (at least after three hours when using phenylglyoxal and phenylalanine amide), the reactions were always allowed to warm to room temperature by removal of the dry ice bath. In all our trials, the two isomers 3

• and Table 2, we undertook optimization trials focusing on the condensation between phenylglyoxal (1{1}) and the hydrochloride salts of either alanine amide (2{1}) or phenylalanine amide (2{2}). In the course of this, many reaction parameters were taken into account (i.e., base addition speed (s

• alanine amide (2{1})) was secured. As listed in Table 2, some of the results of the reaction optimization studies using compounds 1{1} and 2{2} followed the trends reported in Table 1. But for entries 16 and 17 in Table 2, a slow addition of the base, at −78 °C, was always used and we also checked that an

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• -phenylphosphinamide (92a) and chloromethyl N,N’-dimethyl-N,N’-diphenylphosphondiamide (92b) via an intramolecular Friedel–Crafts alkylation. Although they tried several different amide derivatives, only phosphinamide 92a and phosphonic diamide 92b gave the corresponding 1-methyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2

• by two step hydrolysis gave the same product 223 in 28% yield. Phosphorus tribromide first reacted with more nucleophilic amide nitrogen atom to form dibromophosphanamine derivative 224 by loss of HBr. The more nucleophilic dibromophosphanamine derivative 224 further underwent a nucleophilic addition

• from P-(chloromethyl)amide precursors 92a and 92b through intramolecular Friedel–Crafts alkylation. Synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N’-diallyl-vinylphosphonodiamides. Diastereoselective synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N

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

• solid state by X-ray crystallography (dimer 2), and implicit solvent QM geometry optimizations. N-(Methylamino)peptoids were found to preferentially adopt trans amide bonds with the side chain N–H bonds oriented approximately perpendicular to the amide plane. This orientation is conducive to local

• -substituted glycines [1][2]. They retain the same backbone as peptides except that the side chains are located on the nitrogen atoms of the amide bonds and thus represent an important class of peptide biomimetics [3][4][5], generally with improved cell permeability [6] and proteolytic resistance [7][8

• -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

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• -2-ene-1-carboxylic acid 2f–i. The amide 2f and nitrile 2g [34] were found to be less active dipolarophiles towards the azomethine ylide 1 than hydrocarbons 2a–e. As a result, the corresponding cycloadducts 3f and 3g were obtained in moderate yields (58% and 55%, respectively) as single diastereomers

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• in the fixed-bed material that interact with the oscillating electromagnetic field. Recently, Rebrov and co-workers disclosed the direct amide formation of a carboxylic acid and anilline using high energy ball milling to prepare the sulfated TiO2 (50 wt %)/NiFe2O4 (50 wt %) catalyst that serves as

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• (40 mol %) in the presence of P(OEt)3 (6 equiv, triethyl phosphite) under air at 100 °C (Table 1). The yield of the corresponding amide 3a was 78% (Table 1, entry 1). The reaction was completely inhibited in the absence of the copper catalyst or P(OEt)3, and no product was detected (Table 1, entries 2

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• showed an amide doublet resonance at 7.09 ppm. On the other hand, the 13C NMR spectra showed all characteristic signals for all of the synthesized compounds, with multiple aliphatic peaks for the cholyl and aliphatic amine moieties. The fingerprint signals for the cholyl moiety (C–OH) were evident in all

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• compounds 8, 20 and 21 albeit in low yields. Due to the extremely low isolated yield of compounds 20 and 21, we looked for an alternative more efficient procedure. In 2008 Sun et al. [32] described a method of karrikin alkylation in position 7 via direct metalation with lithium bis(trimethylsilyl)amide

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• amide functionality [13][14][15][16][17][18][24][25]. At the same time, norbornadiene derivatives are available from metalated substrates. Hence, norbornadiene is deprotonated with the Schlosser base and subsequently trapped by an appropriate electrophile [26][27]. In addition, halogenated norbornadiene

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• under the assumption of a shared biosynthetic origin. Compound 6 shows an optical rotation of = −10.6, which is consistent with the published value of pseudomonin A ( = −9.5) [12]. This natural product is structurally closely related to 6, featuring a terminal amide instead of a carboxylic acid