Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• of toxic agents such as MeI, TFA, or sodium cyanoborohydride can be harmful to both health and environment. Additionally, the need for constant protection and deprotection steps is time-consuming and results in low atomic economy, while also increasing the use of solvents, energy, and chemicals

• [34]. In reductive amination, the substrate is usually an aldehyde or amine. After the formation of the iminium ion, it is reduced with the appropriate reagent to form the N-methylated amino acid. Different methods have been established using for example benzaldehyde as a protection group, sodium

• cyanoborohydride as a mild reducing agent, and paraformaldehyde as a methylating agent [36]. Methanol can be used as the methylating reagent in other methods. Here, a palladium on carbon (Pd/C) catalyst processes the dehydrogenation of the alcohol to form the corresponding aldehyde. The subsequently formed imine

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• 6). This result indicated that borohydride reagents were able to activate the thiazole moiety in [1,3]thiazolo[4,5-b]pyridines, leaving the pyridine unit unchanged. While sodium cyanoborohydride afforded a comparable result, albeit with lower conversion, the use of silane reagents at elevated

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

• sodium cyanoborohydride and trifluoroacetic acid to yield the thermodynamic product 32.4 or sodium cyanoborohydride and trimethylchlorosilane (a bulkier reagent) that favor the formation of the kinetic product 32.3 (Figure 32). Then, a quite similar sequence (the order was different) can be applied to

New synthesis of a late-stage tetracyclic key intermediate of lumateperone

• Mátyás Milen,
• Bálint Nyulasi,
• Tamás Nagy,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66

• to the hydrazine derivative 4, followed by a Fischer indole synthesis with ethyl 4-oxopiperidine-1-carboxylate (5) provided tetracyclic compound 6. Its reduction with sodium cyanoborohydride in trifluoroacetic acid (TFA) to cis-indoline derivative (±)-7, followed by N-methylation [(±)-8] and

• reduced with sodium cyanoborohydride in acetic acid to cis-indoline derivative (±)-35. Removal of the trifluoroacetyl group to (±)-36 followed by N-methylation with formaldehyde and sodium cyanoborohydride gave target compound (±)-9a. It has to be mentioned that the preparation of compound 31 has been

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• ., sodium borohydride, sodium cyanoborohydride, or sodium triacetoxyborohydride) in methanol. Unfortunately, formation of the desired N-acetyl-3-hydroxyoxindole was not observed at all, because a base-catalyzed addition of methanol to the C3=O and subsequent intramolecular rearrangement of the acetyl group

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• converted to oximes 11 and 12 via oxidation with chromium trioxide followed by treatment with hydroxylamine hydrochloride. 11 and 12 were reduced by sodium cyanoborohydride and the resulting hydroxylamines were converted in nitrones, after heating under reflux. These nitrones were not isolated but subjected

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• -Chloro- and 2-bromocyclohexanone were synthetized as previously described [38][39], to provide cis-2-chloro (Cl) and cis-2-bromocyclohexylamine (Br), respectively, by a reductive amination [40]. To a sealed tube were added the corresponding ketone (10 mmol), ammonium acetate (100 mmol) and sodium

• cyanoborohydride (10 mmol) in methanol (30 mL) and the mixture stirred for 48 h at room temperature. To the mixture was added concentrated HCl until pH ≈ 2, forming a white precipitate (protonated amine), which was filtered and dissolved in distilled water, which was washed with CH2Cl2 (3 × 20 mL). To the aqueous

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• -dihydronicotinamide adenine dinucleotide (NADH), NaBH4 reduces NAD+ to a mixture of the 1,2-, 1,4-, and 1,6-NADH isomers [65][66]. Recent attempts to reduce substituted pyridinium salts using less powerful and more selective sodium cyanoborohydride also failed to produce 1,4-DHP derivatives in good yields [56]. As a

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• addition of less than one equivalent of the sodium borohydride as well as the use of tetramethylammonium borohydride or sodium cyanoborohydride, but none were overly successful. Indeed, a representative assay (dry THF, 24 hours at 0 °C, 0.7 equivalents of NaBH4) led to the isolation of 49% of compound 3ae

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• salts. The use of tetramethylammonium borohydride did not increase the overall yield of 6n, however, a rather substantial improvement was observed when using sodium cyanoborohydride. Indeed, from pure acrylate 2n, a 70% yield of 6n was obtained, and in one pot starting from aldehyde 3n, a 48% overall

• yield of 6n was achieved. Moreover, without using an inert atmosphere for the initial condensation between furfural (3n) and ethyl nitroacetate (4) the overall yield of 6n dropped to 37% even when using sodium cyanoborohydride. The optimized conditions were then applied to aldehyde 3r and afforded a

• when using sodium cyanoborohydride instead of sodium borohydride in some cases. This actually illustrates the sensitivity of this reduction which, along with the condensation, are quite limiting. As described above, the recourse to cycloaddition-based approaches allowed us to explore some original

Visible light-mediated difluoroalkylation of electron-deficient alkenes

• Vyacheslav I. Supranovich,
• Vitalij V. Levin,
• Marina I. Struchkova,
• Jinbo Hu and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2018, 14, 1637–1641, doi:10.3762/bjoc.14.139

• with blue light is described. The reaction involves radical addition of 1,1-difluorinated radicals at the double bond followed by hydrogen atom transfer from sodium cyanoborohydride. Keywords: difluoroalkylation; organofluorine compounds; radical addition; visible light; Introduction Applications of

• energetic UV light (xenon arc lamp) in combination with sodium cyanoborohydride to trigger the reaction of non-fluorinated alkyl iodides [45][46][47]. Subsequently, we showed that silyldifluoromethyl iodide can generate the corresponding gem-difluorinated radical in combination with an N-heterocyclic

• light emitting diodes. The use of sodium cyanoborohydride provided a moderate yield of product 3a and about 60% conversion of 1a (Table 1, entry 1). The addition of pyridine notably increased the yield, presumably, by scavenging boron species with a B–I bond formed in the reaction (Table 1, entry 2

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• % yields and is recommended for the substrates containing sulfur atoms, for which transition metal-induced reactions fail. Keywords: diarylmethanes; diarylmethanols; 1,3-dithiane; selective reduction; sodium cyanoborohydride; zinc iodide; Introduction In last decades, diarylmethanes, such as I–IV and

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• position gave the product 12b in 66% yield. In C-6 position both a methoxy and a phenyl group were well tolerated giving 57% and 73% yield of products 12c and 12d. The pyridine directing group could be cleaved by alkylation of the pyridine nitrogen using methyl triflate followed by reduction with sodium

• cyanoborohydride to deliver the N–H unprotected pyridinone 13 in 74% yield (Scheme 4) [29]. A rearrangement of the N-oxide furnished the corresponding isoquinolone 14 in 62% yield. Conclusion In summary, we have developed the C-6 selective C–H heteroarylation of pyridin-2-ones using indoleBXs as coupling partners

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• presented reductive alkylation consists of a reaction of amine 4 with the appropriate aldehyde, which results in the respective imine subsequently reduced with sodium cyanoborohydride to the alkylated amine. Thus, the reaction of 4 with 1.5 molar excess of acetaldehyde followed by the in situ reduction with

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• problem in the alkylation of the sulfonamide 3a, the sequence of steps was reversed. Thus, 2-iodo-N-(4-methoxybenzyl)anilines 7a–g were prepared by reduction of the Schiff bases obtained from 2-iodoanilines 1a–g and 4-methoxybenzaldehyde with sodium cyanoborohydride in a mixture of glacial acetic acid and

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• ). During this study we observed common byproducts related to the reductive amination of sugars [19] (Scheme 1). All the reaction conditions tested (Table 1) showed the presence of alditol 4 as a result of sodium cyanoborohydride lack of selectivity [20] to reduce imines in the presence of aldehydes. When

• and homogenized. pH 11 was adjusted with TEA and finally sodium cyanoborohydride (2 equiv) was added in a single portion. The flask was tightly closed immediately. This mixture was placed in a 100 °C glycerin bath and stirred for 5 hours. Hereafter the media was concentrated under reduced pressure

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• succeeded in a Nickel catalyzed thiolation of aryl iodides with thiourea in DMF. Aryl iodides firstly reacted with thiourea in the presence of bis(triethylphosphine)nickel(II) chloride and sodium cyanoborohydride as catalyst precusor, and afforded aryl isothiuronium iodide, which could be further converted

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• mixed with one of the four complementary template strands (TC, TG, TT or TA, Table 1) in a 1:1 molar ratio. All four nucleobase aldehydes (GCHO, CCHO, ACHO, TCHO) were added in excess amount and in equimolar concentrations. Sodium cyanoborohydride (NaBH3CN) was used for irreversible conversion of the

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• reaction mixture was stirred for 24 h. A yellow precipitate appeared. Then sodium cyanoborohydride (217 mg, 3 equiv, 3.45 mmol) was added and the reaction mixture was stirred for 1.5 h. The reaction mixture was quenched with water (20 mL) and extracted with dichloromethane (3 × 20 mL). The organic layers

Hydrogenation of unactivated enamines to tertiary amines: rhodium complexes of fluorinated phosphines give marked improvements in catalytic activity

• Sergey Tin,
• Tamara Fanjul and
• Matthew L. Clarke

Beilstein J. Org. Chem. 2015, 11, 622–627, doi:10.3762/bjoc.11.70

• triacetoxyborohydride or sodium cyanoborohydride can be appealing at small scale where the practical issues noted above are not so important. However, the formation of tertiary amines from aryl ketones using hydride reagents has been reported to be problematic [31]. In addition, the hydride reductions, whether carried

Synthesis of the pentasaccharide repeating unit of the O-antigen of E. coli O117:K98:H4

• Pintu Kumar Mandal

Beilstein J. Org. Chem. 2014, 10, 2724–2728, doi:10.3762/bjoc.10.287

• reductive opening of the benzylidene acetal on treatment with sodium cyanoborohydride in the presence of HCl/Et2O [25] furnished p-methoxyphenyl 3-O-acetyl-6-O-benzyl-2-deoxy-2-phthalimido-β-D-galactopyranoside (5) in 77% yield over two steps (Scheme 1). Trisaccharide acceptor 11 could be synthesized

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• GAU CCG UG) corresponding to the 3'-terminal sequence of the envisaged RNA-library. The RNA was oxidized by treatment with sodium periodate [42], and the resulting dialdehyde was reacted with cytidine derivative 1. The obtained intermediate was reduced with sodium cyanoborohydride to form the more

• cytidine derivative 1. Peak III indicates the RNA–cytidine 1 conjugate. B: Cytidine derivative 1. C: 20mer model RNA after treatment with sodium periodate and reduction with sodium cyanoborohydride in the absence of cytidine derivative 1. r. I.: relative intensity. Supporting Information Supporting

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• imine (Schiff base), which was subsequently reduced to PEG-g-chitosan with sodium cyanoborohydride [55], allowing retention of net charge. PEGylation can also be accomplished by condensation of the free amino groups with activated PEGs, such as PEG-NHS or PEG-p-nitrophenyl carbonate, converting the

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• 2 equivalents of cinnamyl alcohol 44 in the presence of 2 mol % of Pd/Xanthpos followed by an esterification using benzyl bromide. Ozonolysis, and reductive amination using excess benzylamine in the presence of sodium cyanoborohydride completed the synthesis. Phosphorines Two phosphorines 47a,b were