Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• dielectrophilic glyoxal-based amidine formation (27, Scheme 10a) [97][98][99][100], aldehyde generation via phenanthrenequinones 28 (Scheme 10b) [101], diketopinic acid (DKPA, 29) conjugation (Scheme 10c) [102], and methylglyoxal (30)-mediated arginine–lysine cyclisation (Scheme 10d) [103]. A different approach

• glycoengineering, and the reader is directed to specialised reviews for in-depth discussions [122][123][124]. Periodate oxidation of the non-reducing end of N-glycans is perhaps the oldest and most straightforward approach to generate an aldehyde biorthogonal handle on a glycoprotein, which can then be subjected

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• complexes. Both terminal and internal alkynes could be inserted, with a wide variety of functional groups including alkyl, aryl, OH, COOH, amide and aldehyde substituents, but not DMAD. The excellent stereo- and regiochemical selectivity could be explained by a bimolecular mechanism, as confirmed by DFT

Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• the protonation and subsequent addition of a nucleophile (H2O) an intramolecular rearrangement facilitated by the proximity of a neighboring nitrogen atom (in position 1 or 8) occurred (see Scheme 3). Elimination of the aldehyde leads to the formation of 1,8-diazafluorene (2), which can be oxidized

• ), ammonium acetate (60.5 mg, 0.79 mmol), and aldehyde (0.20 mmol) in glacial acetic acid (5 mL) was heated to 110 °C with stirring for 12 h. The resultant solution was cooled to room temperature and neutralized with aqueous ammonia solution (25%) to pH 6. The precipitate of a product was filtered off and

• washed sequentially with water, methanol, hexane, then dried in air. General method (A2) for the condensation in other acidic conditions A mixture of diazafluorene (30.0 mg, 0.18 mmol), ammonium acetate (60.5 mg, 0.79 mmol), and aldehyde (0.20 mmol), glacial acetic acid (0.02 mL, 0.36 mmol), ethanol or

Preparation of 3-(alkylamino)imidazo[1,2-a]pyridine-2-carbaldehydes via Kornblum oxidation and unexpected ring-opening reactions of the corresponding alcohols under oxidative conditions

• Sandile J. Mkhize,
• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2026, 22, 763–770, doi:10.3762/bjoc.22.58

• -chloroaniline. Alternative oxidation conditions such as PCC, IBX or T. versicolor laccase applied to the alcohols led only to oxidative ring-opening to give oxalamide derivatives, with no aldehyde being isolated. Keywords: 3-aminoimidazo[1,2-a]pyridine-2-carbaldehydes; Groebke–Blackburn–Bienaymé reaction

• ), using conditions described by Gladysz et al. [24]. Reaction with glyoxylic acid as the aldehyde component has previously been reported to yield the 2-unsubstituted product as a result of in situ decarboxylation [25]. Unexpectedly, on product isolation we discovered that compounds 13a–d, the methyl

• -chloroaniline, followed by reduction; ii) reaction of the corresponding carboxylic acid with 2-chloroaniline under peptide-coupling conditions followed by reduction; and iii) reduction of the ester to the aldehyde, followed by reductive amination to give compounds 8. Initial attempts at direct conversion of

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• iminoester 1 with tert-butyl acrylic acid ester 4 occurs first. This is followed by condensation of pyrrolidine 9 with cinnamic aldehyde (10) to form azomethine ylide B, which enters into a second diastereoselective 1,3-DC with various electrophilic alkenes. The authors used acrylic acid esters, vinylphenyl

• azomethine ylides derived from glycine ester and aromatic aldehyde, catalyzed by titanocene dichloride, was studied for the first time (Scheme 28). This catalyst demonstrated a number of advantages, including mild reaction conditions, short reaction times, improved yields, and high regio- and

• due to the possibility of cycloaddition at the carbon–oxygen double bond (C=O) of the aldehyde, which acts as an alternative to the carbon–carbon double bond (C=C) [83]. In 2016, Sridharan reported a one-pot iridium-catalyzed three-component dehydrogenation/1,3-dipolar cycloaddition cascade reaction

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• corresponding triflate using triflic anhydride, followed by Suzuki–Miyaura cross-coupling with phenylboronic acid to give 16 in 59% yield (Scheme 1). Boc removal from intermediates 11–14 enabled attachment of the αD binder aldehyde 16 via reductive amination. Interestingly, NaBH(OAc)3 had performed well in the

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• hydrogenated with 20% v/v hydrogen to afford the desired product quantitatively (Table 3, entry 1). A cyclic ketone 1i was converted to 2i in 84% yield with 10% v/v hydrogen and in 97% yield with 20% v/v hydrogen (Table 3, entries 2 and 3). An aliphatic aldehyde 1w was also hydrogenated to give the product in

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• Liu and co-workers [81]. Regioselective deprotection, oxidative cleavage, reduction with NaBH4 and Bn-protection afforded 50, which was subsequently transformed to aldehyde 51 via ozonolysis and treatment with SMe2. Next, HWE reaction and acidic treatment triggered the cyclizations towards enone 53

• . Protection of the free alcohol unit enabled the transformation towards 55, which involved the reduction of lactone to lactole, protection of the alcohol as acetate, BF3·Et2O-mediated C-allylation of the aldehyde (via oxocarbenium intermediate) and cyclization (oxy-Michael reaction). Hydroboration–oxidation

• , stereoselective dihydroxylation with AD-mix β and diol-protection yielded acetonide 57. Another DMP-oxidation, followed by HWE reaction, and deprotection of the diol motifs enabled the cyclization towards 60. After TBDMS-protection and reduction to the respective aldehyde (62), an alkylation with the α-sulfonyl

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• . Compound 968 is a benzo[c]phenanthridine, made by a three-component cyclocondensation reaction between the 1,3 diketone dimedone, the aryl aldehyde 3-bromo-4-dimethylaminobenzaldehyde, and 2-naphthylamine. This reaction producing the benzo[c]phenanthridine core was first reported in the late 1960s [23][24

• unrealized. This result places the cyclocondensation reaction that generates compound 968 within a family of three-component reactions of 1,3 dicarbonyl compounds, an aryl aldehyde, and various 1,3 di-nucleophiles (Figure 4). These reactions proceed by an aldol condensation between the dicarbonyl and

• aldehyde, followed by conjugate addition and cyclo-condensation with a 1,3 dinucleophile. Members of this reaction family are variations on the Biginelli and Hantzch reactions, where the dinucleophile is urea and the ammonia adduct of a second equivalent of the dicarbonyl, respectively [31]. A similar

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• (±)-4 with yields in the range of 58–92% when the aromatic aldehyde was substituted with either electron-withdrawing (NO2) or electron-donating (alkoxy) groups. It is worth noting that aldehydes bearing oxidant-sensitive substituents, which are incompatible with peroxide-based approaches commonly

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• of propargyl alcohol 3 and the alkyne moiety in 3 can be introduced by an alkynylation of the formyl group of aldehyde 4. Thus, we started this synthesis from O-protected 2-bromobenzyl alcohol derivative 5 for the introduction of the propanal moiety of 4 by a Heck reaction with allyl alcohol. The

• synthetic route for the C6-iodo-substituted 1ad is shown in Scheme 2. The Heck reaction of O-TIPS-protected 5a with allyl alcohol in the presence of a palladium catalyst provided the aldehyde 4a in 78% yield [9]. The reaction of 4a with CBr4 and PPh3, followed by treatment with n-BuLi, afforded the terminal

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• , and even the bulky 2-(2-bromoethyl)-1,3-dioxane, which contains a masked aldehyde moiety, are suitable alkylating agents for the process, providing products 4h–k in good overall yields. The possibility to vary alkyl halide in the second stage of the synthesis opens opportunities for further

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• carbocation 34c, which collapses under an 1,2-alkyl shift to reveal the key intermediate in gibberellin synthesis, gibberellin A12 aldehyde (35). Alternatively, the ent-kaurene core is known to be likely oxidised at C-1 [85] by a thus far unknown biosynthetic oxidation to deliver a secondary carbocation 35a

• Scheme 33B [194]. The proposed precursor 136, with a hydroxy group at C-7 was thought to undergo elimination to form a 6,7-olefin 136a which can be oxidatively cleaved to, in turn, reveal dialdehyde 136b. Aldol addition towards the C-6 aldehyde and elimination of the aldol adduct to form a 5,6-olefin

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• reactions catalyzed by diverse agents (Scheme 1). For instance, in 2013, Shi et al. described a three-component reaction involving 4-hydroxyquinolin-2(1H)-one, an aromatic aldehyde, and Meldrum’s acid, catalyzed by ʟ-proline under heating [37]. In the same year, Kurosh Rad-Moghadam and co-workers developed

• 1,4-addition. No condensation products were obtained and the reaction mixtures consisted solely of starting materials. It is likely that under these conditions, the nucleophilicity of 4-hydroxyquinolinones was insufficient to attack the aldehyde carbonyl, preventing product formation (Scheme 4F

• presumably proceed through in situ formation of the Michael acceptor from the condensation of an aromatic aldehyde with Meldrum’s acid, followed by decarboxylation and lactonization to yield the pyranoquinolinedione products (Scheme 1). We hypothesized that employing an alcohol as solvent could induce

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• -bromo-2-nitrobenzaldehyde (4), which can then be directly converted into 1. However, oxidation of the tolyl methyl group into an aldehyde has proved an ongoing challenge. Several syntheses have used a chromium(VI) oxidation to yield the desired product, but the toxic nature of this reagent and the

• expense of waste treatment raise issues [8][9][11][12]. Others have produced the desired aldehyde by formation and subsequent hydrolysis of a nitrone, a route which requires four distinct steps, making it less desirable [13][14][15][16][17]. While there have been several syntheses of 1 using 3 as a key

• synthesized compound 3 via nitration of 5, it was necessary to oxidize its methyl group to an aldehyde to yield 4-bromo-2-nitrobenzaldehyde (4). We sought to accomplish this transformation by first using a benzylic bromination of 3 to yield 4-bromo-2-nitrobenzyl bromide (6), followed by a Kornblum oxidation

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• enolized carbonyl compound to an imine derived from an aldehyde or ketone and an amine, has been known for more than hundred years [1] and it has become an important method for creating C–C bonds [2][3][4]. The obtained Mannich bases exhibit a broad spectrum of biological activities [5][6] and have also

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• (±)-dihydrolysergic acid (Scheme 11). Smith and co-workers recently reported a six-step synthesis of (±)-lysergic acid [77]. In contrast to previous approaches, the pyridine was introduced via a magnesium–halogen exchange of pyridyl iodide 93, followed by addition to aldehyde 94. Subsequent reduction of the resulting

• brilliant dearomatization strategy (Scheme 15) [83]. Starting from a para-disubstituted benzene 107 and an unsaturated aldehyde 108, they obtained 109 via a Staudinger aza-Wittig reaction. Compound 109 isomerized to the internal salt 110 in the presence of TFA, and 110 spontaneously underwent two different

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• group in the α-position (e.g., aldehyde, ketone, sulfone, nitro) is beyond the scope of this review. In 2011, Guinchard and Roulland reviewed Pd-catalyzed cross-couplings of 1,1-dichloroalkenes and boron-chlorination reactions in the context of natural product synthesis (Figure 3C) [33]. Takai’s

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• moiety was introduced as a precursor to an aldehyde, which was obtained by reduction of 46 to 47. For the right-hand fragment (ring D, E, and F), an asymmetric hydrogenation of α-substituted acrylic acid 48 was performed, followed by redox manipulations to give aldehyde 49 over 3 steps in 95% and an

• formation and reductive coupling with an aldehyde made accessible β-amino alcohol 60 over two steps. A cascade reaction occurred upon treatment with HCl in acetone followed by treatment with KOH. Indeed, a tandem 5-exo-trig cyclization, sulfinyl removal, and lactamization occurred in one-pot. Finally

• retrosynthetic cut in the Zhu/Gao group synthesis of veratramine [25] proceeds through the C-ring (Scheme 18). Key highlight of this synthesis poses the photoinduced excited-state Nazarov cyclization (44 → 45). The cut for the convergent coupling divides the molecule in a left-hand AB-fragment with an aldehyde

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• ]. Some rhodanine-based derivatives act as inhibitors of hepatitis C virus (HCV) protease [19], UDP-N-acetylmuramate/ʟ-alanine ligase [20], histidine decarboxylase [21], aldose/aldehyde reductase [22], fungal protein mannosyl transferase 1 (PMT1) [23], metallo β-lactamase [24], cathepsin D [25], JNK

• aldehyde 1, activated by protonation of the oxygen atom through structure ii, forming the intermediate aldol iii. In the presence of EDDA, water elimination occurs in intermediate iv, yielding the Knoevenagel adducts 3 or 4. Synthesis of novel imidazo[1,2-a]pyridine–thiazolidinone hybrids To further

• , hybrid compounds combining the imidazo[1,2-a]pyridine scaffold with the thiazolidine nucleus were synthesized. Initially, aldehyde derivatives of the GBB adducts 8 were prepared from 2-aminopyridines 5, terephthalaldehyde (6), and isocyanides 7 using a green methodology that employed phosphotungstic acid

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• then converted to vinyl iodide 26 via hydrazine formation followed by iodination using Barton’s method. Subsequent Bouvealt aldehyde synthesis and in situ reduction delivered allylic alcohol 27. Epoxidation of 27 with m-CPBA afforded the rearrangement precursor 28. Protonic acid-promoted semipinacol

• enantioenriched compound 33, a nickel-catalyzed hydrocyanation of the terminal alkyne was performed. Subsequent protection of the tertiary alcohol with TESOTf and reduction of the resulting cyanide to an aldehyde afforded compound 34 (Scheme 4). Addition of isopropenyllithium to aldehyde 34, followed by TES

• deprotection, afforded enal 42. To avoid the chemoselectivity issues in the subsequent allylic oxidation and radical cyclization steps, enal 42 was converted to 43 by reduction of the aldehyde and protection of the resultant diol with Ph2SiCl2. Allylic oxidation of 43 with 44 [37] afforded the enone in 22

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• , smoothly constructing the A ring to afford compound 14. Subsequent protection of the vicinal diol and aldehyde functionalities in 14 provides an intermediate that, after Baeyer–Villiger oxidation and subsequent tungsten-promoted reverse epoxidation, forms lactone 15. Ozonolysis of 15 cleaves the double

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• smoothly to deliver the aldehyde which was immediately subjected to the condensation reaction with benzylhydroxylamine. The corresponding nitrone 10 then underwent an intramolecular cycloaddition. Adduct 11 was isolated as the major product in 42% yield for 2 steps. Comprehensive NMR analysis revealed the

• from the use of crotyl bromide as a mixture of geometric isomers. After installation of the crotyl group, hydrolysis of the acetonide group and oxidative cleavage of diol 16, oxime 17 was prepared through the condensation of the aldehyde with hydroxylamine in overall 59% yield. Upon oxidation with

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• in a stable aldehyde 23. This aldehyde is a product of intramolecular aldol–croton condensation and can be used in the synthesis of bartsioside (24) or its analogues [21][22] (Scheme 4). The authors [19] performed similar oxidative transformations with Diels–Alder adduct 25 obtained from LG and

• Me2S to give dialdehyde 28 and reaction of compound 28 with colloidal potassium in toluene. During aldol condensation in the presence of morpholine-camphorsulfonic acid (CSA) or ʟ-proline, a stable aldehyde 30 was isolated in yields of 50% and 75%, respectively. Decarbonylation and corresponding

• allylic oxidation using H2SeO3-dioxane system to form the C30 aldehyde 47, or by the ozonolytic cleavage of the double bond between C20 and C29 to produce 20-methyl-3-ethyldiketone 48 [36]. Intramolecular nitrile–anionic cyclization of ketone 46 or diketone 48 under conditions of basic catalysis proceeded

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• . This intermediate was intended to be prepared through allylation [36] with its precursor 15 accessible from aldehyde 16 and acetyl chloride through ketene–aldehyde [2 + 2] cycloaddition [37]. Results and Discussion Our synthetic route commenced from the known aldehyde 16 which is readily accessed in a

• single step from commercially available fructone [38] (Scheme 3). Following an efficient O-trimethylsilylquinine-catalyzed ketene–aldehyde cycloaddition and subsequent alkylation [36], 17 was synthesized. From 17, it was envisioned that the bicyclic skeleton could be efficiently constructed through ketal