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

• compounds 44 (Scheme 21), subsequent phosphorylation of the alkoxide with electrophilic phosphate triesters yielded the phosphate esters 44 in ca. 40–50% yield, after purification by flash chromatography on silica gel (0–10% methanol in dichloromethane as an eluent). These products were then oxidized using

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• the corresponding secondary cyclopropenylcarbinol (S)-1f (ee = 99%), which in turn is readily available by applying the Sharpless kinetic resolution procedure to (±)-1f [31], was also investigated. The resulting geometric isomers (Z)-3f and (E)-3f, which were separated by flash chromatography, were

• (TFDA) [68] to a solution of propargyl glycolates 64a–n containing NaF in diglyme at 120 °C. Difluorocyclopropene 65a could be purified by flash chromatography on silica gel and was isolated in 86% yield but this compound rapidly underwent decomposition upon storage. The instability of glycolates 65a–n

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction

• Yue Zhong,
• Wen-Yu Wu,
• Shao-Peng Yu,
• Tian-Yuan Fan,
• Hai-Tao Yu,
• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26

• were monitored through UV light. Flash chromatography was carried out on silica gel 300–400 mesh. 1H and 13C NMR spectra were recorded in CDCl3 at 500 and 126 MHz, respectively, using the solvents as internal standards. High-resolution mass spectra were taken on Waters Synapt MS. The peak patterns are

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• EtOAc were purified by distillation. All other commercially available solvents were used without purification. Thin-layer chromatography was carried out on silica gel 60 F254 (Merck). Column chromatography was performed on silica gel 60 (70–230 mesh, Merck). Flash chromatography was performed on Büchi

• : dichloromethane/methanol 10:1). The mixture was cooled to room temperature, diluted with toluene (15 mL), and acetonitrile was removed in vacuum. The toluene solution was then filtered through a short pad of Celite, the filtrate was concentrated, and the residue was purified by flash chromatography

• (TLC monitoring: dichloromethane/methanol 10:1). The reaction mixture was then cooled to room temperature, diluted with toluene (5 mL), and acetonitrile was removed in vacuum. The remaining toluene solution was passed through a short pad of Celite, concentrated, and the residue was purified by flash

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• of primary amines 12a–f with ynones 11a and 11b. aFollowing concentration in vacuo, further purification using silica gel flash chromatography was required. Cyclisation of precursors 13 to natural product analogues 14 using palladium- or copper-catalysed conditions. Yields quoted are isolated. a13ab

A novel and practical asymmetric synthesis of eptazocine hydrobromide

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan,
• Kuaile Lin and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• organic layers were washed with water (100 mL × 2), dried, filtered and evaporated under reduced pressure to dryness. The residue was purified via flash chromatography with dichloromethane/methanol (20:1) to give 14 as colorless oil (2.15 g, 45.5%). 1H NMR (400 MHz, CDCl3) δ 8.07–8.05 (d, J = 8.0 Hz, 1H

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• of the trityl ether providing known alcohol 16 [34]. Treatment of 15 with TBAF yielded identical alcohol 16 in good yield. As described by Trajkovic et al. [34], oxidation of alcohol 16 with DMP led cleanly to the desired aldehyde 17. As some decomposition products were formed during flash

• chromatography on silica gel, the sensitive aldehyde 17 was used in the next step without further purification and characterization. Diastereoselective addition of MeMgBr to the aldehyde group of 17 gave alcohol 18 as single diastereoisomer in 69% yield. Removal of the Cbz protecting group of 18 under catalytic

Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• stoppering or catenation of such atropoisomeric pseudorotaxanes. Experimental ESI(+)–MS measurements were performed on a Micromass Bio-Q triple quadrupole mass spectrometer equipped with electrospray ion source, using a mixture of H2O/CH3CN (1:1) and 5% HCOOH as solvent. Flash chromatography was performed on

First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

• Grzegorz Mlostoń,
• Katarzyna Urbaniak,
• Paweł Urbaniak,
• Anna Marko,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2018, 14, 1834–1839, doi:10.3762/bjoc.14.156

• . In addition to anthraquinones 2b and 2c, the simple 1,4-benzoquinone (2a) was also tested in the reaction with thiochalcones 1. The reactions performed with 1a and 1b delivered the expected 4H-thiochromene-5,8-diones 4m,n, which were isolated in good yields using flash chromatography, but underwent

• menadione (2e) was completely consumed. The solvent was evaporated in vacuo and the crude mixtures were analyzed by 1H NMR first and subsequently purified by flash chromatography using dichloromethane (for 4a–n) or a mixture of petroleum ether and dichloromethane 1:1 (for 6) as the eluents. For products 4a

Heterogeneous acidic catalysts for the tetrahydropyranylation of alcohols and phenols in green ethereal solvents

• Ugo Azzena,
• Massimo Carraro,
• Gloria Modugno,
• Luisa Pisano and
• Luigi Urtis

Beilstein J. Org. Chem. 2018, 14, 1655–1659, doi:10.3762/bjoc.14.141

• , the mixture obtained by reacting 1f with 1.1 equiv of 2 and 3 mol ‰ of NH4HSO4@SiO2 in 2-MeTHF under dry Ar was filtered and dropwise added to a vigorously stirred freshly prepared solution of EtMgBr in the same solvent at rt. Aqueous work-up and flash chromatography afforded the desired tertiary

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• ending up with 2.9 g of enriched methanol extract. This extract was purified further by Si-Flash chromatography (Grace Reveleris®) using an 80 g silica column, with dichloromethane (DCM)/acetone solvent gradient of 25% to 100% acetone in 23 min followed by 100% acetone for 13 min. This resulted in 9

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• 7, and could be easily isolated by flash chromatography in 91% yield. A shortening of the reaction time to 1 h profoundly increased the amount of byproduct to 52% (Table 1, entry 8). Surprisingly, the desired product 3 could be isolated in 58% yield from this experiment after prolonged storage of

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

• Dandan Li,
• Naoya Oku,
• Atsumi Hasada,
• Masafumi Shimizu and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2018, 14, 1446–1451, doi:10.3762/bjoc.14.122

• second fraction was then further fractionated by ODS flash chromatography and purified by HPLC to yield the eight metabolites 1–8. The molecular formula of 3 was established as C18H23NO based on a HRESITOFMS measurement (m/z 270.1855 [M + H]+, Δ +0.3 mmu). Analysis of 1H, 13C, and HSQC NMR spectra in

• successively partitioned between 60% MeOH (250 mL) and CH2Cl2 (250 mL × 3) and the latter between 90% aqueous MeOH (150 mL) and n-hexane (150 mL × 3). The aqueous MeOH layer, which concentrated the antibacterial activity against Tenacibaculum maritimum, was subjected to ODS flash chromatography (Ø 3 × 7 cm

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• cycle was collected and evaporated. Then the mixture was acidified with 3 N HCl and extracted with EtOAc, dried and concentrated in vacuo. The synthetic precursor of FPID 6 could be purified by flash chromatography in order to remove excess Fmoc-protected amino acids during the peptide coupling

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• concentrated under reduced pressure before purification by flash chromatography. General procedure B: bromo(trifluoro)acetoxylation To a solution of the geranyl derivative (1.0 equiv) in acetonitrile (0.07 M) cooled to 0 °C, PIFA (1.1 equiv) was added. A solution of tetra-n-butylammonium bromide (1.1 equiv) in

• , dried over MgSO4, filtered and concentrated under reduced pressure before purification by flash chromatography. General procedure C: bromohydroxylation To a solution of the geranyl derivative (1.0 equiv) in acetonitrile (0.1 M) cooled to −10 °C, DIB (1.4 equiv) was added. A solution of lithium bromide

• (1.6 equiv) in H2O (0.1 M) was then added dropwise over 5 min. After stirring at −10 °C for 10 min, the reaction mixture was diluted with EtOAc, filtered over alumina (EtOAc) and concentrated under reduced pressure before purification by flash chromatography. General procedure D: iodo(trifluoro

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• aminations at C-2 or C-4 in the 13α-estrone series. Reactions were performed on a 0.25 mmol scale with 1.2 equiv of amine, 10 mol % Pd(OAc)2, 10 mol % X-Phos, at 100 °C, 10 min under microwave irradiation. Flash chromatography yields are reported. Two-step synthesis of 2-amino-13α-estra-1,3,5(10)-trien-17

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

• Morten M. C. H. van Schie,
• Tiago Pedroso de Almeida,
• Gabriele Laudadio,
• Florian Tieves,
• Elena Fernández-Fueyo,
• Timothy Noël,
• Isabel W. C. E. Arends and
• Frank Hollmann

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

• with DCM. The collected organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the isolated mixture was performed by flash chromatography on silica (pure DCM). The final product was obtained as colourless oil (200 mg). (E)-Hex-2-enal TLC (DCM) Rf 0.9; 1H

Enhanced quantum yields by sterically demanding aryl-substituted β-diketonate ancillary ligands

• Rebecca Pittkowski and
• Thomas Strassner

Beilstein J. Org. Chem. 2018, 14, 664–671, doi:10.3762/bjoc.14.54

• )propane-1,3-dione (495 mg, 1.4 mmol) were added, and the mixture was stirred for 24 hours at room temperature and then for six hours at 110 °C; all volatiles were removed in vacuo, the crude product was washed with water and purified by flash chromatography (silica gel, DCM/isohexanes 3:1). Afterwards, it

• (II) (300 mg, 0.8 mmol) together with potassium tert-butanolate (180 mg, 1.6 mmol) and the β-diketonate 1,3-bis(2,3,5,6-tetramethylphenyl)propane-1,3-dione (540 mg, 1.6 mmol). The crude product was washed with water, isolated by flash chromatography (silica gel, DCM/isohexanes 4:1), and washed with

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• residue was purified by flash chromatography (hexanes–ethyl acetate, 70:30) to afford pure product 15 (318 mg, 1.02 mmol, 63%) as a white solid. TLC [hexanes–AcOEt (2:1)]: Rf = 0.3; [α]D22 +28.5; 1H NMR δ 8.18 (d, J = 9.3 Hz, 2H, ArH), 6.99 (d, J = 9.3 Hz, 2H, ArH), 6.03 (ddd, J5,4 = 6.0 Hz, J5,6 = 10.7

• cooling to rt, water (15 mL) and DCM (15 mL) were added, the layers were separated, and the aqueous one was extracted with DCM (3 × 10 mL). Combined organic solutions were washed with water (10 mL) and brine (10 mL), dried, concentrated, and the crude productwas purified by flash chromatography (hexanes

• , the layers were separated, and the aqueous one was extracted with DCM (3 × 10 mL). Combined organic solutions were washed with water (10 mL) and brine (10 mL), dried, concentrated, and the product was isolated by flash chromatography (hexanes–ethyl acetate, 25:75) to afford 24 (120 mg, 0.08 mmol, 64

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• 6b–d highlighted the diastereoselection of the reaction was highly dependent of the starting benzamide substitution, 44 to 60% de being obtained for 3b–d. Finally, whereas diastereoisomers issued from 6b could be separated by flash chromatography, this was not possible for products 3c and d

• . Cyclisation of chiral benzamides (R)-7a–e and (R)-8 led to isoindolinones (2R)-4a–e, (2R)-5 in good yields and average to good diastereoselectivities (Scheme 3). In some cases, purification by flash chromatography afforded products 4b, 4c and 5 in higher diastereomeric purity. In order to access to the

• isoindolinones (3S)-1 and (3S)-2. Synthesis of parent benzamides 6–8. Synthesis of isoindolinones 3a–d, 4a–e, 5; isolated yield, de by HPLC and 1H NMR. aAfter flash chromatography on silica gel (EtOAc/hexanes 3:7) and crystallization from hexanes/toluene; bafter flash chromatography.on silica gel (EtOAc/hexanes

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• was purified using flash chromatography with DCM/Et3N/MeOH 95:3:2 to give a white solid (0.263 g, 78%). 1H NMR (600 MHz, CDCl3) δ 8.48 (d, J = 5.4 Hz, 1H), 7.93 (d, J = 5.4 Hz, 1H), 7.70 (d, J = 9.2 Hz, 1H), 7.34 (dd, J = 8.8, 7.3 Hz, 1H), 6.39 (d, J = 5.4 Hz, 1H), 4.96 (d, J = 7.5 Hz, 1H), 3.70 (sx

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• monoester, without further purification by flash chromatography. Chloramphenicol-base-derived bifunctional organocatalysts. Design of new chloramphenicol base amide organocatalysts. Synthesis of bifunctional amide catalysts 7a–q. Asymmetric synthesis of (S)-GABOB (13). Conditions screening for asymmetric

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• exhibit axial chirality [21], as has been demonstrated by 1H NMR spectroscopy using the optically active shift reagent Eu(hfc)3 [19]. The enantiomers of the dicarboxylic acid 11 have been separated by flash chromatography of their diastereomeric salts with 1-phenethylamine, and the structures of the acids

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• isomers had to be separated by flash chromatography. In 2014, Sano and co-workers reported a selective synthesis of Xaa-ψ[CF=C]-Pro with a new cyclopentanone derivative 20 bearing a bulky 2-(4-methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl) group (OBO), which favoured the formation of the (E)-isomer in the

• starting from the commercially available protected chiral hydroxyl ester 75. Reduction to the aldehyde followed by coupling with bromodifluoropropene gave two diastereoisomers 76a and 76b separable by flash chromatography. Then, the copper-catalyzed defluorinative allylic alkylation using Grignard reagents

• -alkylation on the γ,γ-difluoro-α,β-unsaturated δ-lactam 86. Unfortunately, the α-alkylation provided a mixture of diastereoisomers 87a and 87b which was separable by flash chromatography. The dipeptide isostere 88 was finally obtained after the opening of the lactam 87b in acidic conditions and N-Boc

An efficient synthesis of a C₁₂-higher sugar aminoalditol

• Łukasz Szyszka,
• Anna Osuch-Kwiatkowska,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2017, 13, 2146–2152, doi:10.3762/bjoc.13.213

• phases were separated, and the aqueous layer was extracted with CH2Cl2 (3 × 20 mL). The combined organic solutions were washed with water (30 mL) and brine (30 mL), dried, concentrated, and the crude material was purified by flash chromatography (hexanes/ethyl acetate 5:1 to 2:1) to afford 13 (0.19 g