Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• ] and provides insights into the biosynthesis pathways of these peptides [14]. However, the biosynthetic gene clusters of compounds 1–4 remain unidentified. Therefore, the least sterically hindered amine, namely the amino group of glycine, was selected as a nucleophile of the cyclization reaction in

• synthesized the necessary building blocks, we turned our attention to construct resin-bound peptide 5 (Scheme 4). The assembly of this hexapeptide started with the loading of Fmoc-ᴅ-Trp(Boc)-OH (6) onto 2-chlorotrityl resin with iPr2NEt, which was followed by piperidine treatment to liberate resin-bound amine

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• )cyclooctane-1,2-diyl dimethanesulfonate. Reaction of the bis(benzyloxy)cyclooctane-1,2-diyl dimethanesulfonate with NaN3 gave 2-azido-3,8-bis(benzyloxy)cyclooctyl methanesulfonate. Reduction of the azide group and debenzylation to give an amine provided the new 3-aminocyclooctanetriol. Treatment of the 2

• relative to the proton H-2. For the synthesis of the aminocyclooctanetriol 13, hydrogenation of the azido alcohol 11 gave amine 12 in 95% yield (Scheme 2). Subsequent, benzyl deprotection with BCl3 of 12 resulted in the target compound 13 in 85% yield. The structures of compounds 12 and 13 are completely

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• work is the phosphonylation of the commercially available bromo-substituted N-aryl precursors bis(4-bromophenyl)amine (Br2BPA), 3,6-dibromocarbazole (Br2DPC), and 4-bromo-N-(4-bromophenyl)-N-phenylaniline (Br2DPPA) (see Scheme 1). In light of using the resulting phosphonic acids as linkers for the

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• constructing azoles with an amine functional group at the 2-position, such as benzoxazole or benzoimidazole, but are unsuitable for the syntheses of 2-arylated or 2-alkylated benzoxazoles and benzimidazoles. In fact, only two reports cover the subject. Jackson et al. carried out the intramolecular ring-closure

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

• . Chiral thiophosphorus acids have been obtained by resolution with a chiral amine as early as 1958 [23][24][25][26][27], or from other precursors [28][29][30]. Having selected chiral thiophosphorus acids for our model study, further design requirements were included (Figure 2) to address some issues

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• and stereocontrol of the reaction depends on the conformational rigidity of the macrocyclic framework and a synergy between the thiourea and tertiary amine sites. Recently, many efforts were focused on the synthesis and applications of mechanically interlocked molecules (MIMs), such as catenanes and

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

• treatment of secondary amine 11 with ene-nitrosoacetal 12 [36] (Scheme 2b). The synthesis of products 7a,b containing two oxime groups was accomplished via double oximinoalkylation of benzylamine to give dioxime 13 [36], cleavage of the N-benzyl group, and reaction of the secondary amine 14 with α

• direction is currently underway. Conclusion In conclusion, we developed a synthetic route to 1,4,6,10-tetraazaadamantanes bearing free and protected amino groups at the bridge N-atoms (N-TAADs). It involves the assembly of a tris(iminoalkyl)amine precursor, which undergoes smooth intramolecular

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• . Common structural motifs include a polyunsaturated acyclic chain with an unsaturated lactone ring and an amine-containing side chain (Figure 1). These natural products have attracted much attention due to their original structure and to their activity as inhibitors of the serine/threonine phosphatase

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

• active site thiohemiaminal (amine to imine oxidation) or disulfide formation, respectively. Additionally, C6–Cl derivative 9 could probe cysteine alkylation. Reported herein is our exploration of this synthesis and the evaluation of GDP 6-chloro-6-deoxy-ᴅ-mannose 18 against GMD. Results and Discussion

• pyrophosphorylation had no positive effect. In the case of no observable reactivity for substrate 13, likely protonation of the amine would result in unfavourable positive charge within the active site and the absence of vital H-bond contacts. X-ray crystallographic data of a related Man-PP from T. maritima show

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

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• example of flavor compounds. The imine bond was chosen for its relative stability; on the other hand, it can be readily hydrolyzed forming the starting non-volatile amine and releasing the aldehyde. The kinetics of the aldehyde release was studied by 1H NMR techniques in buffers with different pH values

• ., easy to follow by TLC. But in the end, the reaction progress was monitored by MS due to the fast hydrolysis of the imine even during the chromatography on TLC plates. Methanol was chosen as a solvent because it dissolves the aldehydes well and sufficiently (≈5 mg/mL) amine 1. At first, we studied the

• , in all cases, a large excess of an aldehyde. Finally, the best reaction conditions for the large-scale preparation of target compounds proved to be just refluxing of amine 1 with up to 30-fold excess of the aldehydes 2a–j in methanol (Scheme 1), which afforded the final imines 3a–j in high yields (80

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• situ to the corresponding amine hydrochloride salt which can be isolated without the use of column chromatography (Scheme 2). The N,N-diborylamines have also been used directly in subsequent transformations [34][35][36][37]. Heptanenitrile was reduced to 1-heptylamine hydrochloride (1a) in good yield

• (83%). This catalytic protocol was applied to the reduction of other aliphatic nitriles to their corresponding amine hydrochloride salts, such as cyclopropyl-bearing (1b, 72%) and branched aliphatic nitriles (1c, 91%). Hexane-1,6-diamine dihydrochloride (1d), a monomer of nylon 6,6 [1], was generated

• , 95%) groups were tolerated under the reaction conditions. The presence of a primary amine in the substrate was tolerated under the reaction conditions (1o), undergoing efficient hydroboration to give the dihydrochloride salt (87%), although an increase in HBpin equivalents (5.5 equiv) was required

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

• thermodynamically controlled basic intramolecular aldol addition of compound 108 using the bulky amine base 2,6-di-tert-butyl-4-methylpyridine (DTBMP) led to epimerization of the methyl group and cyclization, giving preussochromone F (109) as single isolable diastereomer probably via transition state XII. The

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

• amines plays a crucial role in organic synthesis [1][2][3][4][5][6]. In one respect, it is relevant to protect the amine group straightforwardly and under mild conditions [7][8]. On the other hand, the formamide and acetamide moieties are found in many active pharmaceutical ingredients (APIs) and natural

• compatible means in the view of a one-pot methodology for preparing isocyanides directly from amines [56]. When the amine 1 was reacted in the presence of Et3N, HCOOH, and p-Ts-Im [58] (Table 1, entry 5), the formamide was accompanied by a significant amount of sulfonamide (formamide/sulfonamide ratio: 70:30

• desired formamide 2 (71% NMR yield, Table S1 in Supporting Information File 1), denoting the input given by imidazole as a promoter of formamide synthesis. Further variation in the ratio of imidazole/formic acid/amine decreases the reaction yield (Table S1 in Supporting Information File 1). These data

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

• either the salt 16a·HCl or the free amine 16a in good to excellent yield (Scheme 3). We also explored the asymmetric catalytic hydrogenation of adduct 14. Our first attempt at the reduction using organocatalyzed transfer hydrogenation was unsuccessful (see Supporting Information File 1). The (R)-Ru(OAc)2

• , entries 1 and 4). Application of ligand (S,S)-methyl-DUPHOS (L3) gave increased ee in the hydrogenation reaction, but the best result (90% ee) was achieved using 6 mol % Josiphos ligand L2 at 35 °C. Following the synthesis of 3-propylnorleucin methyl ester (16a), we carried on with the amine couplings

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• -Trisubstituted pyrrolidine-2,3-dione derivatives were prepared from the above mentioned 2-pyrrolidinone derivatives and aliphatic amines, which exist in enamine form and are stabilized by an intramolecular hydrogen bond. A possible reaction mechanism between 3-pyrroline-2-one and aliphatic amine (CH3NH2) was

• derivative 4a (1 equiv) and aliphatic amine 9a (2.5 equiv) in glacial acetic acid [42] resulted in the formation of product 10aa with a yield of only 36%. It is clear that compound 9a could be protonated in the acidic environment, decreasing its nucleophilicity and therefore, product 10aa was obtained in low

• yield. The yield of 10aa could be increased to 62% when substrate 4a was reacted with the amine 9a in DMF at 95 °C (Table 4), meaning that the reaction does not require an acidic medium. Ethanol was also used as green solvent to test the above model reaction. As compared to CH3COOH, heating compounds 4a

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• the compatibility of the conversion with a diverse set of alkynes. Reduction of the starting material 11a to quinoxalin-2-amine as a side product was observed in some cases (see Supporting Information File 1 for details). The wide range of tolerated alkynes allows the installation of functional groups

• - (14o) functionality can also be applied for various other reactions. Possible modifications of compounds 14 were exemplarily shown for 14j, which was converted to the amine-substituted product 14j* via nucleophilic substitution with a yield of 77% (see Scheme 3). However, alkynes 4 with reactive and

• reaction to take place. The increase of the amount of catalyst did not significantly improve the yield, while the addition of a base (DIPEA) or Lewis acid (AlCl3) resulted in suppression of imidazole formation and almost complete conversion to the amine 17. Addition of Zn(OTf)2 reduced the yield of the

Synthesis, optical and electrochemical properties of (D–π)₂-type and (D–π)₂Ph-type fluorescent dyes

• Kosuke Takemura,
• Kazuki Ohira,
• Taiki Higashino,
• Keiichi Imato and
• Yousuke Ooyama

Beilstein J. Org. Chem. 2022, 18, 1047–1054, doi:10.3762/bjoc.18.106

• the compounds in the ground state were made using the PM5 method. Dipole moments and HOMO and LUMO energy levels of the compounds were also evaluated from INDO/S calculations. Synthesis 7,7'-(1,3-Phenylenebis(thiophene-5,2-diyl))bis(9-butyl-N,N-diphenyl-9H-carbazol-2-amine) (OTK-2) and 7,7'-([2,2

• '-bithiophene]-5,5'-diyl)bis(9-butyl-N,N-diphenyl-9H-carbazol-2-amine) (OTT-2): A solution of 1 (87 mg, 0.137 mmol), 1,3-diiodobenzene (14 mg, 0.041 mmol), and Pd(PPh3)4 (2 mg, 0.001 mmol) in toluene (1 mL) was stirred for 29 h at 110 ºC under an argon atmosphere. The reaction mixture was diluted with water

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

• reactions occurred. Although the N-methylamine could be prepared from carboxylic acid or amine by our method, the methyl source was remarkably different (Scheme S1, Supporting Information File 1). For amines, the carbon source of the methyl group is from the carbonyl group of the carbonyldiimidazole; while

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

• azodyrecins (Scheme 2). The pathway is likely initiated by Ady2, a putative dehydrogenase that recruits fatty acids from primary metabolism to generate an aldehyde, which would be converted to an aliphatic amine by the pyridoxal phosphate (PLP)-dependent transaminase Ady4. The amine would be N-hydroxylated by

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

• amine) on the most electrophilic component of the α-ketoaldehyde (its aldehyde) to give intermediate 5. However, the ensuing cyclization (via a hydration of its imine bond to allow for a rotation) would then lead to compound 4 which is rarely the major reaction product. Since compound 3 is the main

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

• -(diethoxyphosphoryl)benzoic acid (198) and amine derivatives. They first converted 2-(diethoxyphosphoryl)benzoic acid (198) into its anhydride 1-ethoxy-3H-benzo[c][1,2]oxaphosphol-3-one 1-oxide (199) by treatment with thionyl chloride under nitrogen. The mixed anhydride 199 was further treated with phosphorus

• pentachloride to generate ethyl (2-(chlorocarbonyl)phenyl)phosphonochloridate (200), which reacted with amine and hydrazine derivatives in the presence of triethylamine, affording the desired 1-ethoxy-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxides 201 but the yields were not reported (Scheme 31) [56]. Two ethyl

• synthetic method showed very limited substrate scope. Only less bulky primary amines underwent the first aza-Michael addition and then intramolecular nucleophilic substitution. However, aromatic amines, aniline, 2,3-dihydro-1H-inden-4-amine, and the bulky aliphatic primary amine adamantylamine did not

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

• ]. Beyond their resemblance to peptides, the obvious interest in this family of peptidomimetics arises from their ease of synthesis by the modular submonomer protocol [9] which enables the incorporation of numerous primary amine synthons in a sequence-controlled manner [10], and application of solid

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• To a suspension of compound 5 (0.274 g, 1 mmol) in dry DMSO (0.3 mL) the corresponding amine (2 mmol; in the case of 8 – the solution of dimethylamine in DMSO) was added. The reaction mixture was stirred at 50–70 °C for 0.5 h, then cooled to room temperature, and poured into ice water (10 mL). The

• of compounds 3–18. Reagents and conditions: (a) ethyl 2-bromoethanoate, TBAB, TEA, 50–60 °C, 0.5 h; (b) oxone, DMF, 40 °C, 0.5 h; (c) corresponding amine, DMSO, 50–70 °C, 0.5 h; (d) H2O, DMSO, 100 °C, 0.5 h; (e) H2O, reflux, 1 h; (f) aqueous NaOH, dioxane, rt, 12 h, then, conc. HCl to pH 2; (g

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

• an aldehyde 5, a secondary amine 6, and a terminal alkyne 7, afforded arylpropargylamines 8 in up to 84% yield under flow conditions (Scheme 7, reaction 2). Microwave irradiation interacted with a thin foil of Cu or Au that served as catalyst inside the glass capillary. The work must be highlighted