Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• fermentations of N. altamirensis DSM 44997 were then carried out to secure sufficient material of the responsible iron chelator(s) for isolation and structure elucidation. The metabolites secreted into the culture broth were recovered post fermentation with the adsorber resin XAD-7. After removal of the culture

• as eluent. Fractions that showed a color change in the CAS assay were pooled and subjected to semipreparative reversed-phase HPLC. This led to the isolation of six CAS active compounds (1–6; Figure 1). The major metabolite 1 (12 mg) was obtained as a slight reddish oil. High resolution (HR) ESIMS

• added to the culture broth to bind the secreted metabolites. The resin was separated from the culture broth by filtration, washed with distilled water, and exhaustively extracted with methanol. Isolation of metabolites 1–6 The concentrated extract was first fractionated by flash column chromatography

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• operations, the incorporation of the in-line purification system allowed for isolation of pure material in approximately 100 minutes (from substrate vial to pure product) on a 1 mmol scale. To determine the effect of scale on the system, 2j was processed on a 2 mmol scale (0.5 g) with no loss in efficiency

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• success. Keywords: amines; decarboxylation; eco-compatible; out of equilibrium; purification; Introduction Isolation of pure amines from reaction mixtures or natural extracts is crucial in modern organic chemistry. However, the most widely applied methods for these purifications have remained unchanged

• since the beginning of the 19th century as highlighted by the Sertürner isolation of morphine [4]. However, after formation of the amine acid (ammonium) salt and separation of the impurities, another separation is required to liberate again the free amine resulting in the undesired generation of waste

• Et3N (Table 1, entry 5). Overall, the TCA-induced purification protocol enables the convenient purification of the initial mixture with the isolation of pure dicyclohexylamine in an 94% yield. The excellent yield observed for the purification technique of this, high boiling amine, demonstrates all the

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• neuroprotective effects [6]. As part of a continuing study of our group targeting at the identification of bioactive natural products from the medicinal plants and endophytes [7][8], the chemical constituents of the stems and roots of W. nutans were investigated. This work resulted into the isolation and

• identification of a new bis-coumarin glucoside 1, together with three known bis- and tricoumarin glucosides 2–4, two flavonoid glycosides 5 and 6, and eleven lignan glucosides 7–17 (Figure 1). Herein, we present the isolation and structural elucidation of these natural products and their in vitro biological

• antimicrobial activities. This is the first report of the isolation of coumarins, flavonoids, lignans and phenylpropanoid glycosides from W. nutans, while compounds 1–3, 8, and 11 was encountered from the genus Wikstroemia for the first time. Our work will enrich the chemistry and structure diversity of natural

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• peaks resulted in the isolation of tenacibactins K (1), L (2), and M (3). Compound 1 was obtained as a pale brown powder. HR–ESITOFMS analysis confirmed the molecular formula of 1 to be C33H61N5O8 based on a deprotonated molecular ion [M − H]− at m/z 654.4449 (Δ + 0.2 mmu for C33H60N5O8) and a sodium

• inoculated flasks were placed on a rotary shaker (200 rpm) at 30 °C for 7 days. Extraction and isolation At the end of the fermentation period, 100 mL of 1-butanol were added to each flask and the flasks were shaken for 1 h. The mixture was centrifuged at 6000 rpm for 10 min and the organic layer was

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• Meldrum’s acid in the presence of EDC·HCl and DMAP, followed by methanolysis of the corresponding adducts [27][28][31][36][37][38]. Reaction of the resulting β-keto esters 2a–h with N,N-dimethylformamide dimethylacetal afforded cycloaminyl β-enamino ketoesters 3a–h. After isolation of compounds 3a–h from

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• reactivated by protonation for further cyclisation steps, while previously discussed intra- and intermolecular hydrogen transfers are not supported. Furthermore, the isolation of the new natural product (2S,3S,7S,10R)-guaia-1,11-dien-10-ol from patchouli oil is reported. Keywords: biosynthesis; DFT

• migrations via I to J would indeed be much easier. The final transformations involving two Wagner–Meerwein rearrangements through G and D can proceed smoothly. Isolation of guaia-1,11-dien-1-ol from patchouli oil Fractionation of patchouli oil by column chromatography resulted in the isolation of the new

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• one pot. The deprotonation step, and the isolation and purification of the intermediate product after deprotection using existing approaches are no longer needed when the one-pot approach is used. Because the stepwise PEG synthesis usually requires multiple PEG elongation cycles, the new PEG synthesis

• stepwise PEG synthesis requires to repeat the PEG elongation cycle multiple times, shortening each cycle from two pots to one pot can make PEG synthesis significantly more convenient, which can render monodisperse PEGs more affordable. In addition, the omission of the isolation and purification of an

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• resulted in the isolation of five new methyl-branched unsaturated fatty acids, (2E,4E)-2,4-dimethyl-2,4-octadienoic acid (1), (2E,4E)-2,4,7-trimethyl-2,4-octadienoic acid (2), (R)-(−)-phialomustin B (3), (2E,4E)-7-hydroxy-2,4-dimethyl-2,4-octadienoic acid (4), (2E,4E)-7-hydroxy-2,4,7-trimethyl-2,4

• days. Isolation of compounds 1–5 Compounds 1–5 were obtained from a culture fermented in A16 production medium with a composition of glucose 2%, Pharmamedia® (Traders Protein, Memphis, TN, USA) 1%, and CaCO3 0.5%. The pH of the medium was adjusted to 7.0 before autoclaving. At the end of fermentation

• , 221.1148; found, 221.1149. Isolation of 6 Compound 6 was obtained from a culture fermented in modified V22 production medium with a composition of soluble starch 1%, glucose 0.5%, NZ Amine, Type A 0.3%, yeast extract 0.2%, Tryptone 0.5% K2HPO4 0.1%, MgSO4·7H2O 0.05%, and CaCO3 0.3%. The pH of the medium

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• 4 and 5 are C9 compounds possibly derived from thermal or photochemical rearrangement of compound 3 or another intermediate. The yield of each product was calculated by NMR and verified by isolation (Figure 2). To test the generality of this process with other functional groups, we prepared and

• pathways involving the intermediacy of 8. To provide additional support for this analysis, and to assess the stability of N-formyl amides formed in this reaction, we irradiated alkenyl amide 10, which contains a 2-phenylethyl substituent that allowed easier isolation of N-formyl 11 (Figure 4). After

• then account for the isolation of the acetylated analogue 9. The photochemical pathway described here represents a formal oxidative olefin cleavage of vinylogous nitroaryl-modified amides and ethers. The pathway adds to the diversity of photochemical pathways known for 2-nitrophenyl systems, and the

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• methyl ethyl ketone (MEK) was as effective. In addition, in situ-generated α-bromo-δ-valerolactone was directly converted into a sulfur-substituted functional lactone without difficulty by reacting it with a sulfur nucleophile in one pot without isolation. This new bromination system is expected to

• filtrate was concentrated under reduced pressure to give crude 3b. To a 50 mL flask were added 3b (used without isolation), benzenethiol 4 (2.4 mmol), DMF (5 mL), and K2CO3 (0.45 mmol), and the mixture was stirred at 25 °C overnight. The resulting mixture was extracted with CH2Cl2 (15 mL × 3). The organic

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• first prepared synthetically before its isolation from natural crude material, employing a stereoselective addition of an aryl Grignard reagent to a five-membered chiral cyclic nitrone derived from ᴅ-arabinose [2]. Its analytical data were consistent with those for the later isolated natural product

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• the logic while depicting comparison with the established series of nucleoside analogues. In chiral synthesis, it is often important to establish the ratio of enantiomers before focusing on the isolation of a specific enantiomer. Therefore, having a good overview on enzymatic and chemical resolution

• nucleoside 1a in a protocol by Vorbrüggen et al. In turn, using STS, this valuable asymmetric synthesis provided the intermediate 65, which led to lamivudine (1). Recently, Chen at al. [62] reported the isolation of the strain Klebsiella oxytoca from soil by a target-oriented process, and it was utilized as

• activation of oxathiolane acetates 35a–d. The reaction was complete after a reduced reaction time and suitable for large-scale production with good yield at ambient temperature (Scheme 39). The usefulness of this method was that even without isolation of enantiomerically pure oxathiolane substrate, the

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• chromatographic purification. A lactam byproduct was detected in a small quantity, the isolation and purification of which proved to be problematic. Further work was directed towards reactions using less hazardous TMSN3 as an azide source. Data for entries 2–8 in Table 1 are showing that trimethylsilyl

• lower in comparison to ketone. Again, the corresponding lactam was identified in low yield, but the isolation of the compound was not accomplished. A reaction in DCM, catalyzed by TMSOTf, appeared to be optimal for the synthesis of conjugated tetrazoles in 69% yield. It was shown that the reaction in

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• the cryogel matrix, and shown benefits of doing this include reinforcing the matrix, increasing rigidity, and accelerating formation of pores [16][60][62]. Cryogels offer solutions to obstacles in current medicinal and therapeutic practices. In particular, specific isolation and characterisation of

• stem cells in cell-based therapies, detection of low levels of biomarkers in the blood (i.e., tumour cells, pathogenic microorganisms, etc.) for disease diagnosis, and general isolation of biological substances for clinical and environmental microbiology hold opportunities for cryogels [13][42][61

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• reduced in a stereoselective manner adopting Luche conditions to provide diol 24 (dr 97:3), which after masking the primary alcohol moiety as a silyl ether, allowed isolation of the desired product 25 in 86% yield. This intermediate possessed the correct chirality on the free secondary alcohol to

• epoxide using vinyl Grignard reagent followed by esterification with acrylic acid (35) proved to be inefficient due to low reproducibility and poor isolation of product 36. The strategy was altered by changing the terminal epoxide 34 to an allylic alcohol (95%) utilizing dimethyl sulfonium methylide

• . Oxidation of the secondary alcohol of this intermediate to its keto derivative was problematic and gave no desired product 42 after considerable experimentations. Eventually, the isolation of 43 marked the end of the synthetic study after treatment of 41 with HF·pyridine, which is the reduced form of 6’-epi

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• microbial sources led to the isolation of Pseudomonas sp. UIAU-6B from sediments collected from the Oyun river in North Central Nigeria. Herein, we report the isolation and structure elucidation of seven secondary metabolites including five new (1–5), and two known phenolic siderophores (6 and 7) [28][36

• × 250 mm) columns, and a mobile phase solvent gradient consisting of H2O (Milli-Q filter water 18 MΩ·cm, Millipore, Germany), 100% MeOH (Sigma-Aldrich, UK), and TFA (Sigma-Aldrich, UK). Bacterial isolation and identification The bacterial strain was isolated from soil sediments collected from the Oyun

• river in North Central Nigeria (8.4799° N, 4.5418° W). The sediment samples were air-dried at room temperature for 48 h. Ten grams (dry weight equivalent) were suspended in 100 mL of sterile distilled water, vortexed at high speed, and 1 mL of diluent was serially diluted (10−2 and 10−4). Isolation of

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• in the isolation and characterization of 14 lignan derivatives including three new neolignan glycosides (1–3), four phenolic glycosides including a new compound (15), and a new cyanoglycoside (16) from the organic extracts. The structures of the new compounds were established by NMR analysis (1H and

• 13C NMR, COSY, HSQC, HMBC, and NOESY), HRMS, and chemical methods. The isolated compounds 1–19 were evaluated for their antineuroinflammatory and neuroprotective activities. In this paper, we report the isolation and structural elucidation of these phytochemicals and their biological activity. Results

• tested compounds showed no activity for the cell lines (IC50 > 10 μM). Conclusion Isolation of phytochemical constituents from the twigs of A. fordii led to the discovery of three new neolignan glycosides 1–3, a new phenolic glycoside 15, and a new cyanoglycoside 16 along with 14 known compounds 4–14 and

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• consisting of a mixture of mono- and bis-arylated products, accompanied by a range of unwanted side products. The complexity of the mixture resulted in the isolation of compound 3a in a rather poor yield of 15% (Table 1, entry 1). Furthermore, this initial experiment elucidated that four equivalents (two per

• effectiveness of our strategy, the necessity of isolating the potentially hazardous diazonium salt may be seen as an important disadvantage. Arylating the quinone starting directly from the aniline in a one-pot procedure would effectively avoid the need for isolation of the potentially explosive salt and

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• investigating the behaviour of different alkylating agents (Table 2). Reactions with alkylating agents with increased steric demand provided products in higher ee (compare Table 2, entries 1, 2 and 3); with 3,5-bis(tert-butyl)benzyl bromide allowing the isolation of oxindole 10Ac in 92% yield and 84% ee. The

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• than 70% of them are produced by the genus Streptomyces [1]. However, intensive and concentrated screening activities on soil actinomycetes resulted in the repeated isolation of known compounds [2], which consequently prompted the exploration of untouched niches, such as extreme environments [3]. The

• actinomycete of the genus Actinomadura. We herein describe the isolation, structure determination, and biological activities of 1‒3. Results and Discussion The producing strain Actinomadura sp. AKA43 was isolated from DSW collected at a depth of −800 m in Sagami Bay, Japan. Strain AKA43 was cultured in A16

• intramolecular Diels–Alder reaction [20][25]. Compound 3 is very likely a biosynthetic precursor of 4. This is the first report on the isolation of a biosynthetic precursor of spirotetronate antibiotics as an innate metabolite from a wild-type strain, while such an intermediate was previously obtained from a

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• with complete conversion, the isolation of the pure product was less straightforward and required a recrystallization from a methanol/water mixture, leading to a moderate yield (56%) due to a partial solubilization of the product 7h. This complication was yet balanced by the practicality of the second

• benzyl (4dh, 57%, corrected isolated yield) ester derivatives but remains limited to reagents bearing a benzyl substituent at the malonic position. In an alternative strategy to circumvent the difficulties linked to the isolation of substituted Meldrum's acid derivatives, we envisioned a complementary

• ) and the use of a slight excess of alcohol 8d was beneficial to the reaction. Finally, carrying out the reaction in only CH3CN allows the isolation of the desired pure compound 4da after a simple aqueous work-up, although in a slightly lower 52% yield (Table 4, entry 10). The scope of this reaction was

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• (7g, Scheme 11). However, dimetathesized product (±)-18c was not formed, and isolation of monometathesized products (±)-18a and (±)-18b (or a mixture thereof) in pure form failed despite repeated attempts of chromatographic separation. Finally, isoxazoline (±)-5 was subjected to CM with 4

• . We also attempted CM reactions of (±)-6 with 8-(allyloxy)-1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorooctane (7g, Scheme 17). However, dimetathesized product (±)-24c was not formed, and isolation of monometathesized products (±)-24a and (±)-24b (or a mixture thereof) in pure form failed, despite repeated

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• better understanding of cellulose’s properties are hindered by its poor solubility in most solvents. Relatively short oligomers with DPs of 6–10 tend to aggregate and precipitate out of solution [54], making isolation of pure samples troublesome. Much effort has been put to tune the synthetic conditions

• suggested that XGs are not essential for the creation of the cellulose network [96]. The complexity and diversity of XGs hinder isolation from natural sources and complicates their description. A significant effort was put towards the development of enzymes for selective introduction of the side chains [97

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• synthesis and isolation of the desired N-1 or N-2 alkylindazole regioisomer can often be challenging and adversely affect product yield. Thus, as part of a broader study focusing on the synthesis of bioactive indazole derivatives, we aimed to develop a regioselective protocol for the synthesis of N-1

• -2-n-pentylindazole derivatives of both indazoles 20 and 21 were largely inseparable (Table 2, entries 9 and 10, respectively). However, preparative thin-layer chromatography (PTLC) did permit the isolation of an enriched sample of the N-1-n-pentyl substituted derivative of indazole 20 for (1H–13C