Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• indole nitrogen in control experiments led to halted reactivity or loss of enantiocontrol. These results suggest the importance of hydrogen bonding between the NH group and the organocatalyst. Bisindoles 142 reacted with ninhydrin-derived 3-indoylmethanol 143 in the presence of the CPA (S)-C22 to afford

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• traces of residual moisture. Reactions were monitored by thin-layer chromatography (TLC) using E. Merck silica gel plates and components were visualized by illumination with short wavelength UV light and/or staining (ninhydrin or basic KMnO4). All aldehydes were distilled right before use. All aryl

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• that ninhydrin (150), as an electrophile, reacts with the enol tautomeric form 153 of pyrazolone 152 to give ninhydrin-substituted pyrazoles 151 in a three-component reaction, as depicted in Scheme 52 [158]. The two-component formation of pyrazolone 156 from acetylenedicarboxylates and phenylhydrazine

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• ninhydrin. Estrone-derived dispiropyrrolidines 43, 44, and 45 were obtained in a regio- and stereoselective manner (ylide attacks by the α-steroidal face) in yields ranging from 66% to 72%. 1,3-Dipolar cyclization of azomethine ylides can also be achieved using (E)-steroidal arylidenes at C-16. In 2014, Liu

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• silica gel 60 F254. Visualisation was performed with UV-light (254 nm) fluorescence quenching, and/or by staining with an 8% H2SO4 dip (stock solution: 8 mL conc. H2SO4, 92 mL EtOH), ninhydrin dip (stock solution: 0.3 g ninhydrin, 3 mL AcOH, 100 mL EtOH) and/or ceric ammonium molybdate dip (stock

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

• and cannot be isolated as individual compounds. At the same time, the reaction of ninhydrin and proline results in the formation of the stable azomethine ylide. This 1,3-dipole demonstrated high reactivity towards diverse cyclopropenes, including parent cyclopropene [22]. Note that the reactions of

• cyclopropenes with azomethine ylides from ninhydrin were also successfully carried out in a multicomponent fashion [23]. Mention should also be made of the recent advances in developing enantioselective approaches to the synthesis of 3-azabicyclo[3.1.0]hexane derivatives. Deng and co-workers reported the first

• (MeOH) in 75% yield. Eventually, the constitution of 3a was unambiguously corroborated by NMR spectra. Given the results of previous studies [22][23] concerning cycloadditions of ninhydrin-derived azomethine ylides to cyclopropenes, it was suggested that the stable azomethine ylide 1 appears to react

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• excellent stereoselectivities (up to 98:2 er, >95:5 dr, Scheme 17) [67]. In 2020, Shi and co-workers reported the chiral phosphoric acid (CPA)-catalyzed enantioselective addition reaction of 3,3'-bisindoles 47 and ninhydrin-derived 3-indolylmethanols 52 for the synthesis of 3,3'-bisindoles 53 with single

• stability of the axially chiral products and found that 3,3'-bisindole scaffolds with a single axial chirality are quite stable because of the bulkiness of the ninhydrin group. They also investigated the rotational barrier of substrate 47 and confirmed that it could be rapidly racemized during the reaction

• forming a hydrogen bond with CPA 15. Moreover, the N–H group of ninhydrin-derived 3-indolylmethanols 52 was crucial in increasing the reactivity and enantioselectivity, but it is not important for ninhydrin-derived substrates to carry out the addition reaction. This suggests that this substrate could

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• thin-layer chromatography (TLC) was carried out on silica gel plates (silica gel 60 F254 aluminum supported plates), and the spots were visualized with a UV lamp (254 nm and 365 nm) or using chemical staining with Brady’s reagent, KMnO4, ninhydrin, iodine, and bromocresol. Column chromatography was

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• the mixture of HBTU, HOBT, and DIPEA (3 equiv/3 equiv/6 equiv) in DMF were added to the resin and shaken for 30 min. The reaction was monitored using a Kaiser test based on the reaction of ninhydrin. After washing with DMF (3 × 2 mL) and DCM (3 × 2 mL), 25% of acetic anhydride in DCM (2 mL) was added

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• an ester bond is present. This toxin was subjected to Edman degradation, but this technique provided no information about the composition of the amino acids, suggesting that the amino group at the N-terminus is modified or blocked. However, this toxin was positive for ninhydrin; thus, a basic amino

• -hydroxydecanoic acid. As described above, a basic amino acid (positive in the ninhydrin test) is present in cichorinotoxin. To confirm the presence of a free amino group, cichorinotoxin (6.0 mg) was acetylated for 6 h at room temperature with Ac2O (1.5 mL) in a mixed solvent (5 mL) composed of CH3CN/pH 9.7 Na2CO3

• Pro skeleton was confirmed by the COSY and TOCSY spectra, as shown in Figure 3. The FA-dhThr-Pro fragment was further supported by the fragment ion at m/z 351 in the FABMS (Figure 1 and Figure 2). As described above, a basic amino acid (positive to the ninhydrin test) is present; thus, the amino group

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• rotations were measured on an Anton Paar MCP 300 polarimeter. Thin-layer chromatography (TLC) analyses were performed on silica gel 60 F254 plates using EtOAc/EtOH 1:1 as eluent and visualizing compounds by exposure to 0.2% ninhydrin solution and UV light or I2 vapor. The transamination reactions were

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• . General procedure for the Kaiser test Few resin beads were taken in a test-tube and 2 drops of each of ninhydrin, phenol and 0.1% potassium cyanide solution were added to the test-tube and heated for 2 minutes at 110 °C in a sand bath. The presence of free amine groups was confirmed by the appearance of

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• , 0.1 M HOBt in DMF (4 times; 2 + 2 + 5 + 10 min), (iii) DMF washing (10 × 0.5 min), (iv) coupling of Fmoc-protected amino acid derivative: DIC:HOBt in DMF (4 equiv each) (1 × 60 min), (v) DMF washing (3 × 0.5 min), (vi) DCM washing (2 × 0.5 min), (vii) ninhydrin or isatin test. The cleavage of Mtt

Solvent-free sonochemistry: Sonochemical organic synthesis in the absence of a liquid medium

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 1850–1856, doi:10.3762/bjoc.13.179

• ninhydrin and dimedone. Both systems were investigated in the complete absence of solvent and without the presence of any grinding media (such as inert silica beads) to help mediate the reaction. The aldol reaction was successfully carried out by twin screw extrusion, as I have reported previously [6]. The

• ultrasonic irradiation at room temperature that is instigating and accelerating this chemical reaction. Further confirmation that sonochemistry is a viable method to carry out solid state organic synthesis was obtained by carrying out an aldol reaction between ninhydrin and dimedone (Scheme 2). The optimised

• indicating that a complete reaction had taken place between a hydroxy group of ninhydrin and the activated methylene of dimedone (Figure 7). This reaction has previously been carried out by twin screw extrusion in the absence of solvent [6], and it was confirmed that the same product was obtained by both

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• stereospecific cyclic adducts. Keywords: L-proline; ninhydrin; sarcosine; spiropyrrolidine; 5-vinylindazole; 5-vinylindole; Introduction The [3 + 2] cycloaddition between azomethine ylides and olefins/acetylene as dipolarophiles is an important reaction to access a number of novel heterocyclic spiro scaffolds

• in the construction of functionalized spiro compounds. We report herein the facile synthesis of novel spiropyrrolidine compounds through a one-pot three-component reaction involving N-substituted vinylindole/indazole, ninhydrin and sarcosine/L-proline. The present multicomponent reaction (MCR) leads

• out by reacting N-alkylvinyl products 3 with azomethine ylide, generated in situ through decarboxylative condensation of ninhydrin (4) and sarcosine (5). The 1,3-dipolar cycloaddition of the ylide with the olefin 3 yielded spiropyrrolidines 7 with regiospecificity (Table 1, entries 1–4). The formation

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• connected by a –N= bridge, and thus has a structural analogy to the colored product Ruhemann´s purple obtained by the ninhydrin reaction with amino acids. A plausible reaction mechanism that involves zwitterions, a Strecker degradation of an intermediate imine and water-catalyzed tautomerizations was

• observation suggests a reaction similar to the “ninhydrin reaction” which is used in the identification/analysis of amino acids [18]. The central part of this reaction is the Strecker degradation [19] of an intermediate imine. The surprising instability of the otherwise robust amino acids upon the formation

• the two camphor sulfonylimine units bound by nitrogen at C3 (Supporting Information File 1, Figure S4). The structure of compound 2 thus resembles very much that of Ruhemann’s purple [24], the compound responsible for the intense color developed in the reaction of ninhydrin with amino acids. Compound

Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso–ene mechanism

• David Porter,
• Belinda M.-L. Poon and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 2549–2556, doi:10.3762/bjoc.11.275

• ninhydrin stain. Flash column chromatography was performed on Davisil Grace Davison 40–63 μm (230–400 mesh) silica gel using distilled solvents. Melting points were recorded on a Stanford Research Systems Optimelt automated melting system and are uncorrected. 1H NMR spectra were recorded on Bruker Avance

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• , Japan), and lyophilized to obtain Lac-β-CyD. The reaction was monitored by TLC (silica gel F254, Merck, Whitehouse Station, NJ). Eluent: methanol/water 9:1 (v/v), indicator: p-anisaldehyde for sugar and ninhydrin for amino groups. The Lac-β-CyD gave 1H NMR spectra consisting of protons of both β-CyD and

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• , tube furnace: Thermolyne Type 21100. Reagents for Kaiser test 1.) Buffer pH 5.5: 36 g of sodium acetate was dissolved in 6.9 mL of conc. acetic acid and distilled water was added until a volume of 100 mL was reached. 2.) 5% ninhydrin solution: 5 g of ninhydrin were dissolved in 100 mL of ethanol. 3

• of the KCN solution (no. 3) and 1 mL phenol solution (no. 4) were added and the suspension was heated at 120 °C (oil bath temperature) for 10 min, 1 mL of ninhydrin solution (no. 2, see above) was added and heated for another 10 min. The solution was cooled to room temperature within 30 min and 5 mL

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• of glycoclusters. Experimental General remarks All reactions in organic medium were performed in standard oven-dried glassware under an inert atmosphere of nitrogen using freshly distilled solvents. CH2Cl2 was distilled from CaH2 and DMF from ninhydrin, and kept over molecular sieves. Solvents and

Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA₂DNA triplexes

• Alex Manicardi,
• Lucia Guidi,
• Alice Ghidini and
• Roberto Corradini

Beilstein J. Org. Chem. 2014, 10, 1495–1503, doi:10.3762/bjoc.10.154

• TLC carried out on 0.25 mm E. Merck silica-gel plates (60F-254) by using UV light as visualizing agent and ninhydrin solution and heat as developing agents. E. Merck silica gel (60, particle size 0.040–0.063 mm) was used for flash-column chromatography. NMR spectra were recorded on Bruker Avance 400

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• plates (Merck, Germany) in the proper solvent systems (see below) and visualized by UV irradiation, ninhydrin (amine groups) or cystein/aqueous sulfuric acid (nucleoside and trityl groups). Preparative silica gel column chromatography, RPC, and cation exchange chromatography were performed using silica

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• solvent systems (see below) and spots were visualized by UV irradiation, ninhydrin (for amine groups) or cysteine/aqueous sulfuric acid (for nucleosides and tryptophan) solution. Evaporations were performed under reduced pressure at 40 °C. The preparative silica gel column chromatography was performed

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• pyrrole-fused isocoumarins, which employs solid-supported silica sulfuric acid (SSA) as catalyst, has been developed. When the mixture of ninhydrin adducts of acetylacetone/ethyl acetoacetate and primary amines was heated on the solid surface of SSA under solvent-free conditions, the pyrrole-fused

• under solvent-free conditions (Scheme 1, present work). Results and Discussion Recently, we have reported that the enamines 3 generated from acetylacetone (1) and amines 2 react with ninhydrin to form the cyclic hemiaminal dihydroxyindenopyrroles 4. Subsequently intermediates 4 produce the pyrrole-fused

• ninhydrin to form Schiff bases. To overcome the above problems we have designed an operationally simple one-pot reaction for the synthesis of pyrrole-fused isocoumarins (5 or 8) from the ninhydrin adducts of acetylacetone/ethyl acetoacetate (6 or 7) [43] and primary amines 2 under solvent-free conditions

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• reaction steps were conducted in flame-dried glassware under an argon atmosphere. Dichloromethane and toluene were freshly distilled from CaH2 and Na, respectively. Dimethylformamide was distilled from ninhydrin. 2-Chlorotrityl resin ChemMatrix resin (0.6 mmol/g), coupling reagents and all amino acids were