Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• mixture with its epimer. An epimerization process was observed when a 0.014 M solution of racemic anti-1 in toluene was stirred at room temperature in the presence of the prolinol derivative A (20 mol %). This process led to a mixture of syn/anti epimers that changed over time and reached a ratio of 1:7

• resulted in a slight decrease in enantioselectivity compared to the result obtained when starting from a 1:2 mixture of syn/anti-1. Scheme 6 presents a possible explanation for the epimerization of the pure rac-anti-1 adduct. The reaction of the more reactive enantiomer anti-(3R,4S)-1 with catalyst A leads

• to enamine E, which epimerizes at C-4 and, after hydrolysis, provides the adduct syn-(3R,4R)-1 with an initial er of 4:96. This diastereoselective epimerization phenomenon promoted by an organocatalyst has not been previously described. The study emphasizes the reversibility of some organocatalyzed

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• -glycosides had to be employed in order to obtain anomerically pure indirubin-N-glycosides. As expected, no epimerization was observed during the base-mediated condensation as no aqueous acid was employed. All products were isolated as the pure Z-configured isomers (determination by NMR, the other isomer was

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• occurring DKPs usually consist only of the ʟ,ʟ-diastereomer, here both syn- and anti-diastereomers were observed. This may be due to slow epimerization due to enolization within the gland or during sample preparation and storage, as the ᴅ,ʟ-diastereomers of proline DKPs are more stable than the ʟ,ʟ

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• epimerization of α-substituted intermediates. The lack of the conserved GM (11) motif preceding the αFG helix, which is highly conserved in other types of reductase-competent KRs, was also observed in A2-type KRs. The absence of this region in the electron density map of the A2-type AmpKR11 [30] may indicate a

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• numerous modified techniques, which established the greener side of the reaction. The use of Lewis acid catalysis in this regard [34][35][36][37][38][39] played a significant role, which also suppressed the epimerization in the case of chiral molecules. Among the various Lewis acid catalysts such as

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• conventional Diels–Alder reactions [95][118][119][120][121][122][123][124]. On the other hand, the initially exo carboxylic acid substituent in the oxanorbornene ring is converted to its endo isomer by epimerization upon heating the cycloadduct in a mixture of pyridine–glacial acetic acid (1:1). In the process

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

• amount of the C-9 epimerization product 11 might be explained by a competing radical oxidation of the organoborane intermediate IM-16 by oxygen when the oxidation step is opened to air [32][33]. On the other hand, an alternative mechanism for the formation of 11 involving the oxidation of the 9-epi-IM-16

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• the other hand, the chemoenzymatic process using purified Sgd TE from its biosynthesis and a linear peptide SNAC substrate gave the macrocycle in an acceptable yield without epimerization (Scheme 3). Although NAC-containing thioesters were widely employed, as described above, it had several

• limitations, such as possible Cα epimerization [45] during SNAC coupling and essential HPLC purification, which was generally difficult and time-consuming. Developing other different methods, exceptionally more straightforward approaches to access activated substrates, would solve this inevitable bottleneck

• at the biomimetic position (17a), which not only alleviated the epimerization in the macrolactamization process compared to other positions, but also enabled investigation of its biosynthetic pathway [60]. They also identified a stand-alone enzyme known as SurE, which is classified as a penicillin

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• : epimerization domain, TE: thioesterase domain, KS: ketosynthase domain, AT: acyl transferase domain, KR: ketoreductase domain, TauD: taurine dioxygenase domain. Substrate specificity of A and KS domains is presented at the top of each module (FA: fatty acyl, Arg: arginine, MM: methyl malonyl, Asp: aspartic acid

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• -specific A-domain; A2, ʟ-Pro-specific A-domain; A3, ʟ-Val-specific A-domain; A4, ʟ-Orn-specific A-domain; A5, ʟ-Leu-specific A-domain; E, epimerization domain; C, condensation domain; TE, thioesterase domain. (A) Adenylation reaction in a nonribosomal peptide synthetase. (B) Structures of aminoacyl-AMS

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

• bond formation. Additional common domains include epimerization (E) domains for converting naturally occurring ʟ-amino acids to ᴅ-amino acids, methyltransferase (MT) domains that typically methylate specific N atoms, and terminal condensation (CT) domains which cyclize the growing peptide chain and

Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• structural analysis of GAGs is extremely difficult due to their complex pattern of modification such as epimerization and sulfation [29]. In addition, GAGs’ high flexibility and periodicity render these molecules profoundly challenging to analyze using experimental techniques only [30][31]. Thus

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

• chromatography. Because 4.6 was obtained in better yields and in only 3 steps, the epimerization of 4.6 to 4.10 was also reported (Figure 4B). This epimerization is achieved in three-step sequence that starts with the double tosylation of 4.6 to produce 4.11. Then, the SN2 reaction with potassium acetate in DMSO

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• nitronate to the α,β-unsaturated iminium ion, should be tackled to improve the diastereocontrol. All efforts to discriminate the two faces of the nitroenolate during the addition proved unproductive during the optimization, therefore, a potential epimerization was envisaged during the course of the reaction

• formation of secondary nitronates. However, it could not be improved to synthetically interesting values. The observed diastereomeric ratio is, therefore, the direct result of the second Michael addition reaction, as previously reported [29], and no post-process epimerization event could be found. With the

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• afford various N-substituted pyrroles 27 in 89–94% yields (Scheme 12). A major advantage of this protocol is that in the case of chiral amines, pyrrole formation proceeds without detectable epimerization. In 2013 Azizi et al. [66] have demonstrated a simple and environmentally friendly protocol for the

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• -mediated epimerization. Guénée et al. described the allylation, benzylation, and propargylation of magnesium enolates. These enolates were generated by a Cu-NHC-catalyzed conjugate addition of Grignard reagents to β-substituted cyclic enones (70) (Scheme 19) [51]. Fox and co-workers developed an intriguing

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• (established via the α-protonation/deprotonation in the intermediate α-carbanion in the amino acid moiety) and concomitant epimerization of the final product [41]. The results of the thiolation of complex (ΔAlaNi)L7 are given in Table 1. The corresponding ʟ-cysteine derivatives (RCysNi)L7 were isolated in high

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• diastereomeric mixture (α-position of the lactone, OTES) (Scheme 11) [36]. Interestingly, in this transformation the G-II-mediated ring formation was performed in the presence of MgBr2, which acted as an epimerization agent at the lactol position yielding compound 67 as a single diastereomer in 65% yield. Of

• instead of 100 °C) to avoid C-7 epimerization, and two equivalents of the Pd complex. The cycloadduct 129 was obtained in very high yield and could be converted to cotylenin A (130) in 5 steps. This work constituted an enantioselective total synthesis of cotylenin A (130) (Scheme 25). 3.2 Intramolecular

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

• the ratio of the minor diastereomers, the ketone mixture was treated with NaOMe, resulting in epimerization of 9, arriving at a 3:3:1 mixture of 9, 10, and 11. Unfortunately, a moderate amount of material was lost due to competing aldol reactions of the ketones. While compound 9 was epimerized to a

• degree of epimerization at C-8a or a less selective Diels–Alder reaction compared to the racemic synthesis. Similar results were obtained within the R-series, starting with R-17. A final Grignard reaction using both ketone stereoisomeric mixtures with methylmagnesium bromide led to the R- and S

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• 167 at 390 nm in the presence of NaHCO3 in CH3CN/t-BuOH, 5:1 to provide 168 in 55% yield (Scheme 14) [91]. Alkylation of the tetracycle, followed by epimerization of the C2 center and radical deoxygenation, or alternatively SN2 etherification, provided the common scaffold 170. The latter can serve as

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• thermodynamically controlled basic intramolecular aldol addition of compound 108 using the bulky amine base 2,6-di-tert-butyl-4-methylpyridine (DTBMP) led to epimerization of the methyl group and cyclization, giving preussochromone F (109) as single isolable diastereomer probably via transition state XII. The

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• was repeated in the presence of an additional base (1 mol equivalent of Et3N); the result was identical to that previously obtained for the equimolar 4:p-tolylthiol mixture (compare entries 1 and 3 in Table 2). Thus, it seems reasonable to suggest that a base may induce epimerization of the product

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• epimeric relationship between 5 and 4. Epimerization at C-10 caused upfield shifts for C-10 and C-1 (δC 71.5 and 142.8 in 4; δC 70.3 and 140.4 in 5), whereas the resonance of C-14 was shifted downfield from δC 30.2 in 4 to δC 31.2 in 5). Further, the diagnostic NOESY correlations between 14-Me (δH 1.54

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• hydrochloride salt, using a protocol developed by Nudelman et al. [51]. Coupling with the protected tripeptides using TBTU occurred without epimerization [52]. The two tetrapeptide allyl esters were subjected to the peptide Claisen rearrangement, the key step of the synthesis. Subjecting allyl ester 8a to the

• usual conditions of an ester enolate Claisen rearrangement with zinc chloride as chelating metal gave the rearranged product in only 33% yield and a diastereomeric ratio of 93:7 (Table 1, entry 1). The reaction was kept at −45 °C overnight to suppress potential epimerization of the peptide. Generally

• , epimerization is prevented through deprotonation of amide NH bonds, as argued by Seebach for Li enolates [53][54]. Nevertheless, isoleucine was prone to epimerize under the reaction conditions due to its vicinity to proline and therewith lack of the “protecting” NH group. Since no full conversion was observed

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• data [72]. Moreover, the epimerization by the conditions of SMC is unlikely as it has been excluded by total hydrolysis of a late-stage SMC modified RGD peptide [67]. Analysis of the secondary structures of the cyclic peptides P2–P4 by CD spectroscopy also did not show a significantly increased α