Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• formation of DBDAP, prompted us to test alternative CO surrogates. When the reaction was performed using Co2(CO)8 (0.3 equiv) in the presence of DBU, the intermediate 3a was isolated in 35% yield, but again no DBDAP 4 was obtained (entry 8, Table 1). Formic acid, an effective CO surrogate [20][22], was also

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• 2.6C18 Packed column (2.1 mm ID × 100 mm, Nacalai Tesque) coupled with a model LCMS-8040 liquid chromatography–mass spectrometer (LC–MS) (Shimazu Corp.). The compounds were eluted with a linear gradient of water/acetonitrile containing 0.1% formic acid. Isolation and structural determination of compound

• -II (10 mm ID × 250 mm, Nacalai Tesque), and the metabolites were eluted with a linear gradient of water/acetonitrile containing 0.1% formic acid. Fractions containing compound 6 were concentrated by evaporation. Compound 6 was then desorbed in DMSO-d6, and the structure was determined by the JNM-A600

• 30 °C for 1 h. After centrifugation, the supernatant was analyzed using LC–MS equipped with a BioResolve RP mAb polyphenyl column (2.1 mm ID × 100 mm, Waters, Milford, MA, USA). The compounds were eluted using a linear gradient of water/acetonitrile containing 0.1% formic acid. In vitro analysis of

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• products) [26]. HPLC: Phenomenex Lux Cellulose-3 column (3 mm, 250 × 4.6 mm), eluent CH3CN/H2O (0.1% formic acid) 40:60, isocratic mode; 0.6 mL min−1; UV detector 222 nm, 30 °C. The retention time for the (S)-enantiomer was 12.3 min, for the (R)-enantiomer 14.7 min. General procedure for recycling of the

• 164.4, 163.9, 135.1, 133.7, 130.7, 129.5, 106.9, 76.1, 49.0, 41.4, 36.8, 36.7, 29.8, 21.8 ppm; HRESI(+)-MS (m/z): [M + Na+] calcd for C17H18ClNO6Na, 390.0720; found, 390.0682; HPLC: Phenomenex Lux Cellulose-3 column (3 mm, 250 × 4.6 mm), eluent CH3CN/H2O (0.2% formic acid) 40:60, isocratic mode; 1 mL

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• transition-metal-based complexes, the outcomes are generally two-electron reduction products, such as carbon monoxide (CO), formic acid (HCO2H), or formate (HCO2−). To mitigate the strong energetic requirements of the reaction shown in Equation 1, the reduction of CO2 occurs in the presence of protons, so

• that the energy barriers of the reactions shown in Equation 2 and Equation 3 are lowered. In fact, the formation of the radical anion CO2−· takes place at −1.9 V versus normal hydrogen electrode (NHE), while the proton-assisted reductions of CO2 to CO and formic acid happen at −0.53 V and −0.61 V

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• -VAP Expert, Germany). HRESIMS spectra were recorded with an Agilent 1200 Infinity Series HPLC-UV system (Agilent Technologies; column 2.1 × 50 mm, 1.7 µm, C18 Acquity UPLC BEH (waters), solvent A: H2O + 0.1% formic acid; solvent B: ACN + 0.1% formic acid, gradient: 5% B for 0.5 min increasing to 100

• : deionized water (H2O) + 0.1% formic acid (FA) and solvent B: acetonitrile (ACN) + 0.1% formic acid. The binary gradient was: linear of 5% B for 5 min, automatic stepwise gradient from 5 to 100% B for 5–105 min, followed by 100% B for 10 min wash, and finally by 80% ACN + 20% H2O for 10 min re-equilibration

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• , followed by cyclization with glyoxal in formic acid. We then wished to slightly perturb the electron density via introduction of fluorine (either at R1 or R3), but it was at this time that an unexpected result was observed. Following the same conditions which produced B1, NMR evaluation of our next product

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• reduction consumed the sacrificial donor methanol to form formic acid and formaldehyde [56]. This system is interesting for a number of reasons. Rather than intermediate redox mediators shuttling charge between two photocatalytic assemblies, Ishitani, Domen, and co-workers covalently connected the catalytic

• photocatalytic or electrochemical carbon dioxide reduction. The oxidation product, formaldehyde, can be re-reduced. However, separation of formaldehyde and the carbon dioxide reduction product formic acid would be difficult. Therefore, a logical route for sustainably sourcing methanol would be using this system

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• , Milford, MA, USA). The solvent system was as follows; deionized H2O + 0.1% formic acid (FA, v/v) (solvent A) and acetonitrile (ACN) + 0.1% FA (v/v) (solvent B). The separation gradient was operated as follows; 5% B for 0.5 min, 5% B to 100% B for 20 min, and 100% B for 10 min. The flow rate was maintained

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• used to trap carboxylic acids, from which the product can be released with diluted solutions of formic acid [95]. Another strategy that is applicable in the context of biocatalysis involves Ni–NTA resins used for protein purification which are commonly packed in cartridges to enable automated peptide

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

• chloroform was treated with a large excess (85–100 equiv) of formic acid at room temperature, we were pleased to observe the formation of bicyclic compound 8 as the major product in 64% yield. Notably, 8 is the ethyl ester of (−)-halichonic acid and features the characteristic 3-azabicyclo[3.3.1]nonane ring

• envisioned for this carbocation (e.g., a nucleophilic attack of formic acid to give a formate ester), only alkene formation was observed in this system. Interestingly, the deprotonation step is completely regioselective, giving the more highly substituted endocyclic trisubstituted alkene found in 8 as

• elimination to form an alkene or intermolecular nucleophilic attack by formic acid (ultimately giving a formate ester) are reasonable mechanistically, only the intramolecular nucleophilic attack by the carbonyl group of the pendent ethyl ester was observed in this system to form the resonance-stabilized

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

• desired triamine 9. After cyclization of the resulting 4-ethoxy-2,3,6-triaminopyridine (9) with formic acid leading to ethyl-protected compound 10 and liberation of the O6 with hydrogen bromide, 1-deazaguanine (11) was formed in 2 to 4% overall yield (Scheme 2) [18]. The approach by Gorton and Shive

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• % formic acid) were employed for the first minute, followed by a linear gradient to 100% MeOH (0.1% formic acid) over 8 min followed by a 1.5 min isocratic elution of 100% MeOH (0.1% formic acid) all at a flow rate of 0.3 mL/min. UHPLC–MS data was analysed using Thermo Scientific Dionex Chromeleon 7

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• ) function as sterol 14α-demethylases in green plants [24][25][98]. These enzymes catalyse oxidation of the C14α methyl group to trigger elimination of formic acid [24][25]. The sister subfamily CYP51H, on the other hand, is only found in monocots. AsCYP51H10 from Avena sativa (oat) is a multifunctional CYP

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

• (Ø = 8 mm, m = 3.2 g) [22][55] in a horizontal vibratory mill at 30 Hz. Under these conditions, we did not detect the formation of the formamide moiety. At the same time, the desired product 2 was obtained in 16% NMR yield when formic acid was added to the reaction mixture (Table 1, entry 2

• mmol of the model substrate with 2.0 mmol of formic acid and 1.0 mmol of imidazole [23], the product was obtained in better yield and with a higher degree of purity. A control experiment performed by reacting p-methoxyaniline (1.0 mmol) and formic acid (2.0 mmol) provided lower conversion into the

• 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

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• g, agar 20 g, distilled water up to 1 L) for 15 days from the above seed culture. Analytical methods All HPLC analyses were performed using (A) H2O with 0.1% formic acid and (B) acetonitrile with 0.1% formic acid at 40 °C column temperature unless otherwise noted. The HPLC–UV analysis of feeding

• , Supporting Information File 1) was collected and further purified by a Shimadzu LC-20AD semipreparative HPLC by using (A) H2O with 0.1% formic acid and (B) acetonitrile with 0.1% formic acid. Compounds 1 (5.0 mg), 2 (2.2 mg), and 3 (2.0 mg) were isolated using a YMC-Triart C18 column (250 mm × 10 mm, 5 μm

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• electrospray ionization (ESI) source (MicrOTOF-QII, Bruker Scientific) in positive mode. The compounds were individually dissolved in a solution of 50% chromatographic grade MeCN and 50% deionized H2O + 0.1% formic acid. General experimental procedure for the synthesis of hydrazones 1a–i In a 100 mL round

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

• the methylation reagents and the reductive amination reactions by using formaldehyde or paraformaldehyde as the “indirect” alkylation reagents [16][17][18][19]. Recently, a variety of promising methylating agents or C1 sources such as formic acid [20][21], methanol [22][23][24][25][26][27][28][29][30

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• safe two-step synthesis of 56 from cyclohexanone. In the first step, a solution of cyclohexanone in dodecane is mixed in a Q-piece with hydrogen peroxide, nitric acid, and formic acid and subsequently pumped at room temperature through a PTFE tube reactor with a residence time of 93 min. The resulting

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• appropriate fraction was collected, evaporated, and purified by preparative HPLC (Shimadzu) over a phenyl-hexyl column (Luna, 5 µm, 250 × 21.2 mm, 100 Å) (eluent: H2O/MeCN + 0.1% formic acid 80:20 to 50:50). The appropriate fraction was collected and evaporated to afford farnesylated 8-HQA. HRMS/MS analysis

• °C using a Luna Omega C18 column (100 × 2.1 mm, 1.6 μm, 100 Å, Phenomenex) preceded by a SecurityGuardTM ULTRA guard cartridge (2 × 2.1 mm, Phenomenex). Mobile phases were acidified with 0.1% formic acid and consisted of H2O (A), and acetonitrile (B) with a flow rate of 0.3 mL/min and the injection

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

• ) [93]. Cyclohexanone (25) was mixed with conc. formic acid, and a mixture of H2O2 (30%)/HNO3 (65%) in a PTFE reactor at rt. This led to the formation of the cyclic triperoxide 91 in 48% (isolated) yield. Interestingly, the equilibrium favors the formation of the trimer 91 over the corresponding dimeric

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• . The monosaccharide of 5 was detected at 13.8 min, the same detection time (13.8 min) as ᴅ-glucopyranoside. LC–MS analysis was perfomed under the following conditions: flow rate 0.7 mL/min; 25% MeCN with 0.1% formic acid, column, Kinetex C18 column (250 mm × 4.6 mm, 5 µm, Phenomenex). Sugar analysis

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• 90% acetonitrile with 0.1% formic acid and 10% water with 0.1% formic acid at a flow rate of 0.4 mL/min. Freeze-drying was conducted on a Scientz-18N freeze-dryer. Synthesis of compound 2. A mixture of compound 1 (2.30 g, 3.7 mmol), ethyl azidoacetate (5.76 g, 44.7 mmol), copper(II) sulfate