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

• derivatives with a C-5 double bond are a base peak at m/z 113 and two characteristic ions, m/z 153 resulting from formal cleavage of the double bond, and m/z 180, resulting from allylic cleavage of the C-7–C-8 bond (Supporting Information File 1, Figure S5) [23][24]. A similar pattern can be seen in the

• the first methyl group was at C-4, due to a missing peak at m/z 178 in the corresponding ion series (Supporting Information File 1, Figure S6). The next visible ion in this series, m/z 232 results from cleavage adjacent to the double bond, and the ion m/z 246 results from allylic cleavage. The 40 Da

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• functionalization method where primary, secondary, and tertiary alkyl radicals can be readily generated through the sequential anodic oxidative fragmentation of alkyl carbazates, enabling the functionalization of N-heteroarenes [7]. This transformation is particularly valuable as the cleavage of the C–O bond to

• oxidized to a carbocation, which is subsequently attacked by the alkoxide to furnish the final product (Scheme 17). The Lei group also demonstrated C–F-bond formations, particularly developing an electrochemical method for the cleavage of C–C bonds and the 1,3-difunctionalization of arylcyclopropanes [26

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• ]. Iodoethane was also shown to be an effective reagent furnishing the product in up to 56% upon heating to 40 °C (Table 1, entries 11 and 12). It was envisaged that oxidation of iodoethane led to formation of oxidized forms of iodide by C–I-bond cleavage, therefore tetrabutylammonium iodide was utilized to see

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• , therefore we were compelled to proceed directly to the next step. Cleavage of the 1,6-anhydro bridges was achieved under acetolysis conditions providing halogenated talopyranoses 12–15 in good yield over 3 steps as α anomers. Luckily, inter-halides 13–15 were crystalline, allowing the absolute configuration

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• Pt cathode and a Mg anode in the presence of carbon dioxide induced reductive C(sp3)−O bond cleavage at the benzylic position in diarylmethanol compounds and subsequent fixation of carbon dioxide to produce diarylacetic acids in good yield. This protocol provides a novel and simple approach to

• diarylacetic acids from diarylmethanol species and carbon dioxide without transformation of the hydroxy group into appropriate leaving groups, such as halides and esters including carbonates. Keywords: C(sp3)–O bond cleavage; diarylacetic acid; diarylmethanol; electrochemical reduction; fixation of carbon

• dioxide; Introduction Electrochemical reduction of benzyl alcohol derivatives can induce reductive cleavage of a C(sp3)–O bond [1] at the benzylic position to generate the corresponding benzylic anion species. This protocol has been frequently applied to electrochemical carboxylation [2][3][4][5][6][7][8

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• cleavage of the methoxyphenyl group in aqueous methanol using excess of ceric ammonium nitrate (CAN) as a soft oxidant (Scheme 14). The sequence afforded the target (S)-homoallylic amine 69 in 64% overall yield with a complete retention of chirality. To gain a mechanistic insight into the formation of the

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• sufficient resolution and depth [52]. In general, cleavable linkers can be divided into two main groups based on the cleavage mechanism, which can be either enzymatic or chemical. The advantage of cleavable linkers is the possibility to combine stringent enrichment, ensured by the biotin–streptavidin complex

• , with the selective release of modified peptide–probe conjugates afterwards. The frequently used enzymatically cleaved TEV-linker contains a peptide sequence, which is recognized by Tobacco Etch Virus nuclear inclusion A peptidase, which is orthogonal to trypsin and chymotrypsin cleavage – two most

• . The fragmentation of the triazole ring leaving the primary amine and b-ion resulting from the fragmentation of the TEV-recognition peptide sequence. The chemical cleavage of the linker to release probe–peptide conjugates is achieved mainly by the change of the pH or via reducing conditions to release

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• time of two days under a pressure of 0.8 GPa [23]. Less reactive benzyl malonates, which allow for the cleavage of a free carboxylic group without the need for harsh base- or acid-mediated conditions [24], undergo additions catalyzed by primary amines [19]. However, these transformations are hampered

Synthesis and reactivity of the di(9-anthryl)methyl radical

• Tomohiko Nishiuchi,
• Kazuma Takahashi,
• Yuta Makihara and
• Takashi Kubo

Beilstein J. Org. Chem. 2024, 20, 2254–2260, doi:10.3762/bjoc.20.193

• O–O bond cleavage to give compounds 1 and 5 (Scheme 2). Owing to the high reactivity of the DAntM radical, cyclic voltammogram (CV) was measured by using the stable DAntM cation, prepared from compound 3 oxidized by antimony(V) chloride, which can be characterized by 1H, 13C NMR, and UV–vis

• formation of a 1,2-dioxetane (DOT) intermediate and decomposition to aldehyde 1 and anthroxyl radical 5 via C–C and O–O bond cleavage. This reactivity is attributed to the predominant localization of an unpaired electron at the central sp2 carbon of the DAntM radical. These findings provide variable

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• reductive cleavage of the C4a–O5 bond in alternariol derivatives leads to biaryls which are thus no longer lactones, the respective derivatives are obviously derived from alternariol and their inclusion in this review seems to be reasonable. Even derivatives downstream in the alternariol biosynthesis, which

• lack the carboxylic acid are included (Figure 13). Altenusin (47) is biosynthetically obtained through reductive cleavage of 4-hydroxyalternariol (19) and it was already mentioned in one of the first reports on Alternaria metabolites when it was isolated from Alternaria tenuis (synonymous to A

• cleavage and further transformations. The isomeric altenusinoides A and B (52 and 53) were isolated from Alternaria sp., where no biological activities were determined so far for these compounds [242]. Altenuene and its diastereomers and substituted derivatives Altenuene and its diastereomers: Altenuene

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• Scheme 7 [56]. In a consecutive process, after removing the protecting groups through acidic cleavage and cyclocondensation with 1,3-dicarbonyl compounds, the corresponding pyrazoles 25 were formed in a one-pot procedure. Interestingly, both β-aminoacrolein and β-aminovinylketones can also serve as

• give 1,5-diacyl-5-hydroxypyrazolines 131. Cleavage of the protecting group with potassium carbonate in methanol finally provides the corresponding 5-acyl NH-pyrazoles 132 (Scheme 46) [149]. A novel approach to synthesizing pyrazoles via the initial formation of isoxazoles 138 through (3 + 2

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• core. For the byproducts, 3a would be generated through the quenching of radical I with a hydrogen atom source. Bisdipyrrin 4a could be formed through the ring-opening reaction of I by the homolytic cleavage of the C(sp2)–C(sp2) bond to radical II, the addition of the isobutyronitrile radical, and

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• step to driving bond formation and/or cleavage. Therefore, the discovery of new modes for activation leads to reaction advancements. Electrochemical [1][2][3][4][5] and photochemical [6][7][8][9][10] reactions that induce single-electron reduction and oxidation are widely used in modern synthetic

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• use of triflic acid (TfOH) resulted also in the cleavage of the alkyl group derived from the isocyanide, with formation of 47 (Scheme 18). Kanizsai et al. [51] have reported the synthesis of 4,5-disubstituted 2-amino-1H-imidazoles and their further modification through the GBB-3CR. The 2

• (IPT)-mediated intramolecular oxidative annulation and a hydroxylamine-induced ring cleavage of intermediate 48. With this one-pot sequential procedure they synthesized 49 in yields up to 95% (Scheme 19). The subsequent GBB-3CR led to the unique 1H-imidazo[1,2-a]imidazole core 50 with 4 distinct

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• physicochemical characteristics, number of predicted cycles (one cycle or more was required), the presence of serine (Ser) and threonine (Thr) residues, and the characteristic cleavage site of the C39 peptidases domain (GG or GA) (Table S2 in Supporting Information File 1) obtained in RiPPMiner [5]. The nine

• Information File 1). Moreover, findings from the MS2 experiment on the fragment with 5 net dehydrations suggested one internal tryptic cleavage between G41 and the C-terminus, with K48 as the likely cleavage site if C64 is macrocyclized (Figure S3, Supporting Information File 1). Antimicrobial activity of

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• of 10% Pd/C and 5% Pd/CaCO3 yielded reduced compound 19. Cleavage of the THP group with Amberlist-15® resin and a final Jones oxidation of the primary alcohol to the carboxylic acid, led to cyclization with the 17β-OH group affording the lactone 20 in a moderate overall yield (Scheme 6). Biological

• synthesis of 2H-furan-3-ones from mestranol [23]. Initially, a 1,3-dipolar regioselective cycloaddition occurred between the alkyne group of mestranol and an alkanonitrile oxide generated in situ from the corresponding oxime, yielding isoxazoles 31. Later, a reductive ring cleavage of the isoxazole ring was

• tert-butylsulfinyl cleavage, yielding the 17-allyl-17-amine hydrochlorides 121a,b diastereomers. These hydrochlorides were then acrylated with acryloyl chloride. When starting from 121a, the bis-acylated compound 122a1 was only detected in traces (3% yield), with the mono-acylated derivative 122a2

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• on a decagram scale in five steps from (+)-limonene oxide (13), involving epoxide manipulation, oxidative cleavage, and intramolecular aldol condensation. Similarly, the right-half fragment, allyl chloride 16, was synthesized from limonene in five steps. Site-selective hydrogenation, oxidative

• cleavage, and intramolecular cyclization provided 15, followed by functional group manipulation to yield 16. The two segments 14 and 16 were assembled by Nozaki–Hiyama–Kishi (NHK) coupling while controlling the regio- and diastereoselectivities to afford intermediate 17 [25]. Site-selective hydroboration

• synthesis of the bis-THIQ alkaloid family, Oguri and Oikawa utilized the NRPS module SfmC to construct a highly functionalized scaffold from amino acid derivatives (Scheme 10) [102]. The total synthesis of 5 from original biosynthetic intermediate 93 requires regioselective amide bond cleavage to remove the

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• % yield along with 14% acetophenone (6) as the major side product (Table 1, entry 1). Acetophenone (6) is thought to be generated by a Norrish type II cleavage of biradical 2a. Changes at the aromatic core, as demonstrated by acetonaphthone 1b, resulted in low conversions (Table 1, entry 2). When

• extending the reaction time to reach full conversion, significant amounts of Norrish type II cleavage were obtained and product 3b was isolated in only 16% yield. This substrate was therefore abandoned. Interestingly, ethyl (1c) and benzyl (1d) substitution was detrimental to the cyclization, indicated by

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• in bacterial natural products. Crocagin biosynthesis starts with formation of the central ring structure, followed by cleavage of the core peptide by peptidase CgnD. The final steps involve N-methylation by CgnL and carbamoylation by CgnI. It is unclear which modification is installed first. CgnL is

• were first identified in 1994, but their BGC was not identified until 2013 [89][90]. The biosynthesis of ustiloxin starts with the UstA precursor, which contains a 16-fold repeat of the Tyr-Ala-Ile-Gly core. Following the cleavage of the precursor into tetrapeptides, the tetrapeptides are cyclised via

• binding domain (CBD) at the N-terminus and an rSAM domain at the C-terminus (Figure 9) [119]. In addition to its different enzyme structure, a distinct mechanism of methylation than the classical SN2 mechanism is employed. Reductive cleavage of SAM generates a 5'-deoxyadenosyl (dAdo) radical, which

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• agarases to be encoded which belonged to the GH-50 agarase family. The enzymes were named AgaA50, AgaB50, and AgaC50. Biochemical characterization of these three enzymes revealed that AgaA50 and AgaC50 generated neoagarobiose products implying cleavage within the agarose polymer (endolytic hydrolysis). The

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• transformation (Figure 3B). Collectively, our experimental observations are in agreement with the proposed mechanistic picture detailed in Figure 3C. The anodically generated Ce(IV) carboxylates are able to undergo homolytic cleavage of the Ce–O bond upon light irradiation. The resulting carboxyl radical would

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• predominant product (see 18i and 18j). In total, 13 groups could be attached to the different triazenylpyrazoles, yielding 18 products (see Table 1). In analogy to reported procedures for cleavage of polymer-bound triazenes [23], we attempted to develop the first protocol for synthesizing pyrazolyl azides 19

• , presumably due to the increased stability of isomer 18 towards acids. This corresponds with the results for the previously reported triazene cleavage to diazonium intermediates and subsequent cyclization to triazine derivatives [3]. In the next step, the obtained pyrazolyl azides were reacted with different

• via copper-catalyzed cross-coupling [29] with an electron-rich aryl substituent was exemplarily conducted to further expand the scope of possible products (see Scheme S2, Supporting Information File 1). We also investigated the scope and limitations of a one-pot reaction for the triazene cleavage and

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• photocatalytic and electrochemical deoxygenation of acids and alcohols has attracted significant attention as the strategic cleavage of the C–O bond is quite challenging and opens up new possibilities for constructing useful compounds [12][13][14]. The use of photogenerated carbon-centered radicals, such as acyl

• and alkyl radicals, has shown great promise in the synthesis and functionalization of various organic molecules [15][16]. These carbon radicals can be generated in several ways. The first and most straightforward method is the homolytic cleavage of labile C–heteroatom bonds, especially alkyl halides

• and acyl radicals and maintaining a high degree of selectivity with respect to the desired outcome are key obstacles to the growth of alkyl and acyl radical chemistry. With this in mind, the emergence of new chemical transformations involving radicals generated via C–O bond cleavage by visible light

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• recyclization is depicted at Scheme 8. Initially, hydrazine molecule is added to double bond of the pyranone ring leading to zwitter-ion A. Further, cleavage of dihydropyranone fragment results in intermediate B. Next, enehydrazine C is formed from compound B through migration of a proton. Then, intramolecular

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• a methoxy group were transformed into the products in good yields (3la–na). 4-(Trifluoromethoxy)iodobenzene also well participated in this reaction, affording 3oa in 65% yield. Aryl iodides having fluoro and chloro substituents underwent selective C–I bond cleavage to provide monoalkylated products