Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• isotope labeling experiments [6], followed by a 2,7-cyclization, afforded C6 cationic intermediate IM-3 with cyclopiane skeleton. Quench of the cation IM-3 with water would give 4, while upon two 1,2-alkyl shifts of IM-3, followed by deprotonation of cation IM-4, would give spiroviolene (1). On the other

• ][20], and fusaterpenol (8, GJ1012E) [17]. A similar 1,2-alkyl shift of IM-10, followed by deprotonation of the formed spirocyclic cation IM-12, afforded 3. Although previous isotope labeling experiments did not support this pathway for spiroviolene cyclization, it should be noted that a subtle

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

• Talaromyces wortmannii ATCC 26942. Heterologous expression reveals that TadA catalyzes the formation of a new fusicoccane-type diterpene talaro-7,13-diene. D2O isotope labeling combined with site-directed mutagenesis indicates that TadA might employ a different C2,6 cyclization strategy from the known

• and TadA use protonation-induced C2,6 cyclization, TadA likely adopts a more asynchronous process to give a neutral intermediate 3 first followed by protonation to form 1, which is different from the highly concerted deprotonation–protonation process employed by MgMS (Scheme 1B). Further isotope

• labeling experiments and density functional theory (DFT) calculations are needed so as to gain deeper insight into the cyclization mechanism of 1. Functional analysis of the cytochrome P450 enzyme TadB Due to the significance of tailoring enzymes in terms of structural diversification and bioactivity

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• since the 1960s [15][16]. Stable-isotope labeling experiments confirmed that ʟ-tyrosine or ʟ-phenylalanine are involved in the biosynthesis of p-terphenyl as metabolic origin. The precursors undergoing deamination are converted to the corresponding α-keto acid, then a quinone intermediate arises by

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• binding site. Here we discuss protein-based solution NMR techniques including classic 1H,15N-HSQC spectra, TROSY variants for large proteins, fast acquisition techniques and specific isotope labeling strategies, as well as the use of 13C-edited spectra and side chain specific spectra for lysine and

• protein. These methods require excess (5–20-fold) ligand together with relatively small protein concentrations (10–50 µM). Further advantages include no size limit for the protein, as well as no need for isotope labeling of the protein, assignment of protein resonances, and elaborate multidimensional NMR

• challenge. This impedes not only the unambiguous assignment of all signals, but it also makes it difficult to gauge which one of the residues with signal overlap is responding to the binding of a ligand. For ligands targeting just one particular type of amino acids specific isotope labeling of just these

Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

• Zhenghui Liu,
• Peng Wang,
• Zhenzhong Yan,
• Suqing Chen,
• Dongkun Yu,
• Xinhui Zhao and
• Tiancheng Mu

Beilstein J. Org. Chem. 2020, 16, 645–656, doi:10.3762/bjoc.16.61

• corresponding aldehydes 36–42 were isolated with yields of 65−73%. Isotope labeling experiments Isotope labeling experiments were conducted to study the mechanism of the reductive carbonylation of aryl iodide with CO and H2 under our optimized conditions, using 13CO and D2 instead of CO and H2, respectively, as

• . Reaction conditions: PhI (1 mmol), RhCl3·3H2O (2.5 mol %), PPh3 (10 mol %), Et3N (1.2 mmol), DMA (2 mL), CO (5 bar), H2 (5 bar), 90 °C, 12 h. Isolated yields of the products are given and the structures were determined by NMR. Detailed information is given in Supporting Information File 1. Isotope-labeling

• of RhCl3·3H2O and PPh3a. Supporting Information Supporting Information File 230: MS spectra of isotope-labeling experiments and characterization of products. Acknowledgements We thank Institute of Chemistry, Chinese Academy of Sciences for the supply of CO gas and corresponding safety protection

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• decade, numerous interdisciplinary studies have addressed the chemical mechanism of CotB2 catalysis utilizing different detection and analysis methods. Meguro and co-workers [41] established the chemical mechanism for the formation of cyclooctatin using isotope labeling experiments (Scheme 1). Recently

• isotope labeling experiments combined with QM calculations. Intermediate G forms via a 1,5-hydride shift from C6 to C10 to generate a homoallylic cation, and the formation of intermediate H occurs due to cyclization to yield a cyclopropyl ring. Intermediate I forms due to isomeric formation of a

• cyclopropylcarbinyl cation, as shown by isotope labeling [41]. QM calculations support this unusual 1,3-alkyl shift that interconverts H and I [38][39]. Finally, the cyclopropyl ring opens by virtue of a nucleophilic water attack, and cyclooctat-9-en-7-ol is formed. Although gas phase calculations shed light on the

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• stereochemical reaction. The cyclization mechanism of CotB2 has been investigated extensively in recent years. By isotope labeling and NMR spectroscopic investigations [35], it has been shown that CotB2 catalyzes the complex regio- and stereospecific cyclization reaction with an unusual carbon–carbon bond

• binding of GGDP and the cyclization reaction. Based on 2H- as well as 13C-isotope labeling experiments a surprising reaction mechanism has been derived (Scheme 2) [35]. Strong support for the proposed reaction mechanism has been predominantly provided by site-directed mutagenesis of amino acids with an

• followed by a 1,5-hydride shift. The sequential 1,2-hydride shift (C to E) route was initially suggested by theoretical calculations, which supported the overall mechanism [33][34], and this was verified via isotope labeling [34]. Such series of two 1,2-hydride shifts have previously been demonstrated

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• resemblance to cadinane-type sesquiterpenes from plants, but is structurally entirely unprecedented in bacteria. Based on its molecular architecture, a possible biosynthetic pathway is postulated. Keywords: genome mining; herpetopanone; Herpetosiphon; isotope labeling; terpene; Introduction Terpenoids

• this observation. First, it was evident that the isotope labeling was incomplete and that the incorporation of non-labeled metabolic intermediates had led to a mixture of isotopologues and isotopomers. Second, the maximal incorporation of eight labeled carbons was not possible if the compound

• herpetopanone pathway. An involvement of Haur_2987 in the biosynthesis of 1 seems highly likely. Conclusion In summary, we have identified a new diterpene from the predatory bacterium H. aurantiacus 114-95T using an isotope labeling strategy and resolved its structure. A plausible pathway for the biosynthesis

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• independent study by Demangel and co-workers, who confirmed by global proteome analysis via stable-isotope labeling with amino acids in cell culture (SILAC) [101] in T cells that mycolactone A/B is a broad-spectrum Sec61 inhibitor [102]. The mycolactone binding site on Sec61 appears to be located near a

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• . erecta Pd e21 using isotope-labeling experiments that revealed its precursor molecules to be glucose-derived erythrose-4-phosphate (10) and phosphoenol-pyruvate (11, Scheme 1). Due to the observed scrambling of the expected labeling pattern in 13, its biosynthesis has to proceed via a symmetrical

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• subdivided into cytochalasins [41] (phenylalanine), chaetoglobosins [45][46] (tryptophan), aspochalasins [47] (leucine), pyrichalasins [48] (tyrosine) or alachalasins [49][50] (alanine). The biosynthesis of cytochalasans was established on the basis of various isotope labeling experiments using cytochalasin

Synthesis of fluorinated maltose derivatives for monitoring protein interaction by ¹⁹F NMR

• Michaela Braitsch,
• Hanspeter Kählig,
• Georg Kontaxis,
• Michael Fischer,
• Toshinari Kawada,
• Robert Konrat and
• Walther Schmid

Beilstein J. Org. Chem. 2012, 8, 448–455, doi:10.3762/bjoc.8.51

• be probed by following the NMR relaxation changes of the ligand (e.g., selective T1 or T2, which reflect the effective molecular weight). Due to this indirect detection scheme no isotope labeling of the protein interaction partners is required and consumption of protein material is reduced. The