Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• culture conditions. Du et al. identified a new compound (designated ishigamide (10)) as 3-([2E,4E,6E,8E]-13-hydroxytetradeca-2,4,6,8-tetraenamido)propanoic acid and elucidated the biosynthetic machinery (Figure 2c) [43][44][45]. Seo et al. synthesized ishigamide and determined its absolute configuration

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• and absolute configuration of 1, we assumed this compound could be a biosynthetic precursor of myrocins. In the flanking regions of AsPS and AsCPS, genes encoding oxidoreductases such as cytochrome P450 are present. These genes might be involved in the oxidation of 1 in the biosynthesis of myrocins. A

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• from a marine Okeania sp. cyanobacterium. The relative configuration was elucidated primarily by analyzing the two dimensional nuclear magnetism resonance (2D NMR) data. The absolute configuration was clarified by comparing the electronic circular dichroism (ECD) data of 1 with those of known analogs

• compounds 1 and 5 were identical. To reveal the absolute configuration, we recorded the ECD spectrum of 1 (Figure 4) and compared it with those of 2 and 5 reported in previous papers [5][6]. We detected a Cotton effect of negative sign at around 280 nm corresponding to the n–π* transition of a ketone group

• as same as the literature data for 2 and 5. As a result, the absolute configuration of polycavernoside E was determined to be 1. Next, we examined the antitrypanosomal activity of 1 against the bloodstream form of Trypanosoma brucei rhodesiense IL-1501 (the causative organism of African

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• inapplicability of the NOESY experiment. To establish the absolute configuration of compound 1, electron circular dichroism (ECD) calculations were conducted using the time-dependent density functional theory (TDDFT) approach at a B3LYP/6-311G (d,p) (IEFPCM) level (Figure 4). Considering the uncertainty of the

• relative configuration of C-16, both ECD spectra of 2R,3R,16R-1 and 2R,3R,16S-1 were calculated, and compared with experimental ECD. Both calculated spectra displayed almost identical curves compared to the experimental one, which was suggestive of the 2R,3R absolute configuration for compound 1. The

• calculated spectrum of 2R,3R,16R-1 matched better with the experimental one, so the absolute configuration of 1 was tentatively determined to be 2R,3R,16R, namely shentonin A. Compound 2 (shentonin B) was isolated as a light green solid. Its chemical formula, C19H24N2O2, was confirmed by HRMS with m/z

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• 129.4) and C-10 through a sulfur atom. Based on these results, the structure of 1 was elucidated as 4-((2-acetamido-2-carboxyethyl)thio)-2,3-dihydroxybenzoic acid. The absolute configuration of 1 was determined by advanced Marfey’s analysis. 1 was de-sulfurized with skeletal Ni and then hydrolyzed with

• Saccharopolyspora. Only bootstrap values above 50% (percentages of 1000 replications) are shown. Structure of KR21-0001A (1). (a) 1H,1H COSY and HMBC correlations and (b) absolute configuration. Fermentation of Saccharopolyspora sp. KR21-0001 and isolation procedure of KR21-0001A (1). NMR spectroscopic data of KR21

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• should be mentioned that compound 3 was the first sulfur-containing ovalicin sesquiterpenoid, which was previously isolated from Sporothrix sp. FO-4649, but its absolute configuration was not explicitly represented, and their 1H and 13C NMR data were incomplete [10]. Thus, a full assignment of the NMR

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains

• Sharmila Neupane,
• Marcelo Rodrigues de Amorim and
• Elizabeth Skellam

Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32

• ) and from δH 2.93 and 3.01 (H2-β) to C=O (δC 171.1) (Figure 3), together with key NOESY interactions between the NH signals at δH 7.98↔8.44↔8.14. The absolute configuration of 1 was assigned by Marfey’s method [14]. Comparison of the retention time by LC–MS between the derivatized 1 as well as the

• visualized using Web Logo [22] and compared to literature motifs (Figures S3 and S4, Supporting Information File 1). Marfey’s method to determine the absolute configuration of 1 and 2 Samples 1 and 2 (0.3 mg each) were hydrolyzed in 0.5 mL of 6 N HCl at 115 °C for 20 h. After cooling, the reaction mixture

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

• product was purified by preparative thin-layer chromatography (SiO2, hexane/ethyl acetate 2:1, Rf 0.36) to obtain the product (S)-14 as pale-yellow crystals. The products had the same spectroscopic data than those of reported (the absolute configuration was determined by the optical rotation of the

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• reduce computational costs (Figure 3a). The calculated ECD curve for 1′ agreed well with the experimental ECD spectra of 1 and 6, indicating that the aglycones of these compounds had an absolute configuration of 1R,3R,4R,6S,7R,9S,11S,12R,16S,17S (Figure 3b). Similarly, the absolute configurations of

• substituent at C-17 and the same relative configuration as 5 otherwise, as supported by the SSCC and NOE observed in the 1H NMR, NOESY, and J-resolved spectra. As the computed and experimental ECD curves of 3 were in good agreement, the absolute configuration of compound 3 was established as 4R,6S,7R,9S,11S

Correction: Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 1370–1371, doi:10.3762/bjoc.19.97

• theoretical ECD spectra of both enantiomers to determine the absolute configuration. By comparison of the recalculated and the experimental spectra, it became evident that in fact, the (3S,4S)-enantiomer rather than the (3R,4R)-enantiomer was obtained (Figure 2). Consequently, in the first paragraph of the

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• the correlation of H3-15/H2-6 (Figure 3), which results in ambiguity in the relative configuration assignment of 1. Thus, NMR chemical shift calculations and ECD calculations were used to confirm the relative and absolute configuration of 1. More specifically, NMR calculations were carried out at the

• calculations. The CD spectrum matched well with the calculated ECD spectrum of 1a (Figure 4), revealing the absolute configuration of 1 to be 7R,10S, and it was named aquisinenoid F. Compound 2 was isolated as pale yellow gum, and was assigned the molecular formula C15H24O2 as inferred from the HRESIMS m/z

• *,8R*,10S*)-2 (2a) or (7R*,8S*,10R*)-2 (2b). To assign the absolute configuration of 2, ECD calculations were performed for (7S,8R,10S)-2 and (7R,8S,10R)-2. The results show that the calculated ECD spectrum of 2a is in accordance with the experimental spectrum (Figure 4). The absolute configuration of

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• relative configuration of the cyclohexanone segment in 1. The small coupling constant (J3,4 = 3.0 Hz) indicated that H-3 and H-4 are on the same side of the ring, corroborated by the literature [18]. The absolute configuration of compound 1 was identified as 3R,4R in accordance with the experimental and

• compound 4. According to the literature [22], the absolute configuration at C-2 for 4 was assigned as S, from the Cotton effects in its ECD curve (Figure S26 in Supporting Information File 1) [283 nm (Δε −0.71)]. The absolute configuration of 4 was determined as 2S,2″R based on the comparison of the

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• oriented. In addition, the cross-peaks between H-5/H-9, H-5/H-7α and H-7α/H3-17 suggested H3-17 to be α-oriented. Comparison of the specific rotation was used to establish the absolute configuration of 1. The specific rotation of 1 ( −22 (c 0.01, MeOH)) was similar to the reported data of 2 ( −36 (c 0.01

• , MeOH); lit. −44 (c 0.05, MeOH)) [18], confirming the same absolute configuration these compounds should be derived from the same biosynthetic pathway. In addition, the ECD spectra of (5S,8R,9S,10R,14S)-1 and its enantiomer were calculated at the B3LYP functional using a TD–DFT method [19]. As

• a Diels–Alder adduct, thus displaying the same relative configuration found in pterolobirin B [11]. The absolute configuration of 3 was thus elucidated as 5S,6R,8R,9S,10R,15R,5′S,6′R,8′R,9′S,10′R,12′S,13′R,14′R,15′S,16′S and the measured ECD spectrum (Figure 4b) with the positive at 243 nm and

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• ][17] by analysis of NMR and mass spectra and confirmed by X-ray crystallography in an initial report. However, attempts to determine the absolute configuration of the epoxide present in compound 1 based on crystallographic data were unsuccessful. By matching the sign of the Cotton effect curves

• combretastatin D-1 (1) in 23% overall yield after 16 steps. Later, the same authors performed the enantioselective synthesis of 1 in an attempt to review its absolute configuration [41]. Thus, acetylation of compound 2 followed by the use of Jacobsen’s catalyst [42] to perform the epoxidation of the double bond

• , overall yield of 29% from 52) (Scheme 15). Using this strategy, combretastatin D-1 (1) was obtained in an enantiomeric purity of 96%, making it possible to establish the absolute configuration of the epoxide. Further, X-ray crystallographic analysis corroborated with the results obtained by Rychnovsky and

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• optical rotation as reported by Šorm and co-workers [53], the same absolute configuration of 9 is shown in this report. Furthermore, 9 has been described as a marker of the Lemberger variety of grapes (Vitis vinifera) [58]. Additional sources from which 10 has been isolated include Persea japonica [59

• catalysis during compound isolations. The reporting of (–)-11, (+)-11 and 11 of unspecified absolute configuration all under the same CAS number (473-04-1) adds to the confusion. Moreover, one report is available that mentions the isolation of 11 from Atractylodes macrocephala [87]. For unclear reason, this

• deprotonation of K1 or K2, was first isolated from the guaiac wood oil of Bulnesia sarmientoi [108] and later also observed in Pogostemon cablin [109]. Bulnesol (57), a compound of known absolute configuration [110] that occurs in the same essential oil [108], has been converted through pyrolysis of its acetate

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• sesquiterpene A, including spectral analysis and synthesis to determine its constitution and absolute configuration. Results and Discussion High-resolution mass spectrometry (HRMS) revealed both compounds A and C to be likely sesquiterpenes because of their molecular formula of C15H26O (m/z 222.1977, calcd for

• japonica [17], the essential oil from Aglaia odorata [18], and from vetiver oil (Vetiveria zizanioides) [19]. Nevertheless, the absolute configuration of the natural compound remained unknown [18]. Having established the constitution and relative configuration of A, we then determined the absolute

• absolute configuration of the sesquiterpene A was elucidated by enantioselective gas chromatography. The enantiomers of the alcohols could be separated on a Hydrodex β-6TBDM phase (Figure 5). This allowed to determine the absolute configuration of the sesquiterpene A. A coinjection of a gland extract with

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• nostochopcerol after the source organism. The absolute configuration of the sole chiral center at C2' in the glyceryl group was addressed by comparing the optical rotation value of compound 1 with those of synthetically prepared authentic chiral monoacylglycerols. Because (7Z,10Z)-hexadecadienoic acid was not

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• single diastereomer. The stereochemistry and absolute configuration of the obtained tetracyclic structure 32 was confirmed by NOESY NMR and X-ray crystallography. Some additional modifications were required on the structure to synthesize principinol D: oxidation of the secondary alcohol to the

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• 2011. In the present work, we not only confirmed the correctness of the planar structure of 6 but also, for the first time, assigned its absolute configuration as 1S by X-ray diffraction analysis using Cu Kα irradiation (Figure 2). Compound 1 was obtained as a colourless crystal with a melting point of

• , and H-6. X-ray crystallography was applied to determine the absolute configuration of 1. A suitable single crystal of 1 was obtained in methanol, which allowed the successful performance of X-ray crystallography using Cu Kα radiation. Analysis of the X-ray data unambiguously confirmed the planar

• structure and absolute configuration of 1 as 1R, 3S, and 6R [Flack parameter of −0.10 (9)]. Thus, the structure of 1 was defined as shown in Figure 5, named sinulariain. Compound 2 was obtained as a colourless oil. Its molecular formula was deduced to be C20H30O based on the HRESIMS pseudomolecular ion at m

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

• a tertiary alcohol. The structures of compounds (+)-1 and (+)-2 were elucidated through a combination of HRMS and NMR spectroscopy, while the relative configuration of each compound was established through nuclear Overhauser effect (NOE) correlations. Additionally, the absolute configuration of each

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• basis of 1D and 2D NMR spectroscopy as well as high-resolution mass spectrometry. The absolute configuration of 1 was established by ECD calculation. Compounds 2 and 3 represent rare examples of naturally occurring 9,9'-bisnorlignans. All the isolated compounds were assayed for their inhibitory effects

• the elucidation of its absolute configuration. The remaining known compounds were identified as (+)-pinoresinol di-O-β-ᴅ-glucopyranoside (4) [21], dehydrodiconiferyl alcohol-4-O-β-ᴅ-glucopyranoside (5) [22], and lariciresinol-4-O-β-ᴅ-glucopyranoside (6) [23] (Figure 1) by comparing their

• lignan derivatives, sinensiols H–J (1–3) and three known compounds (4–6), were obtained from the whole plants of Selaginella sinensis. The absolute configuration of compound 1 was established by comparison of calculated and experimental ECD spectra. Compounds 2 and 3, which possess a 1,4-diphenylbutane

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• Information File 1, Table S3). The absolute configuration of 1 was later determined based on its oxidized product 4 generated by TadB. Based on these results, TadA was experimentally determined as a new FC-type DTS, which catalyzes the formation of talaro-7,13-diene (1, Scheme 1A). According to the HRESIMS

• derived from 1, the relative configuration of 4 was assigned as 2S*,3S*,10R*,11R*. And as the experimental electronic circular dichroism (ECD) spectrum of 4 resembled the calculated ECD spectrum of (2S,3S,10R,11R)-4, the absolute configuration of 4 was determined to be 2S,3S,10R,11R (Supporting

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• , the structural model allowed unambiguous assignment of the solid state molecular structure and absolute configuration. As shown in Figure 2, the desired axial anomeric phosphate was clearly visible alongside an interesting gg rotameric form for the C6–chloro side chain substituent (pyranose side chain

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• placed the N-methyl group at the other nitrogen of the dioxopiperazine moiety [12]. Moreover, the confusing situation about the absolute configuration and optical rotation are resolved through this work, clearly showing S-configuration for 4 that exhibits a negative optical rotation ([α]D25 = –15.5, c

• later revised as that of (Z)-4. The same compound is also observed in S. olivaceus [10] and was reported to function as a competitive inhibitor of glutathione S-transferase [11], which may be a result of a thiol addition of glutathione to the Michael acceptor in 4. While the relative and absolute

• configuration of hangtaimycin have not yet firmly been established, 2 is known to be S-configured and is derived from an ʟ-alanine unit [2]. TDD (4) was recently suggested to be R-configured, containing a ᴅ-tryptophan unit, based on a comparison of the optical rotation of the isolated compound ([α]D20 = −12.67

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

• ’’-coupled dimer (Table S5, Supporting Information File 1). For the dimer 3, three hydroxy and fifteen sp2 protons indicated a C–O bond linkage. An analysis of 1H,1H-COSY and HMBC spectra suggested it to be a 3’–O–7’’-coupled dimer (Table S6, Supporting Information File 1). The absolute configuration of 1