Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• JohnPhos (6) induced cyclization, yielding bicyclic compound 7 with a 7-membered heterocycle. Final deprotection of the methoxymethyl (MOM) group in 7 afforded (+)-heliannuol D (8). Having successfully applied PPL-catalyzed acetylation to the synthesis of (+)-heliannuol D, the Shishido group subsequently

• 62% ee. A two-step conversion of 34 gave diol 35, which underwent Prins/Friedel–Crafts tandem cyclization to construct tetracyclic compound 36. Final deprotection delivered (+)-brazilin (37). Candida antarctica lipase (CAL) CAL is a type of lipase originating from the yeast Candida antarctica and

• in intramolecular [7-exo] and [8-endo] cyclization, furnishing the 7-membered cyclic ether 40 and 8-membered cyclic ether 41, respectively. Finally, MOM deprotection produced (−)-heliannuol D (42) and (+)-heliannuol A (43). In 2002, Chênevert and co-workers completed the total synthesis of (S)-α

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• -triazoles 28 can be obtained by click chemistry (Scheme 6B) via one-pot deprotection of 26 and Cu(I)-catalysed reaction with an azide [43][44]. Heteroarylimines 31a,b can be easily obtained by condensation of a (hetero)aromatic aldehyde 30a,b with a (hetero)aromatic amine 29a,b [36][37][38] (Scheme 7). The

• reductive cross-coupling of benzyl halides when substituents prone to reduction (CN, esters) are present (Scheme 12C). The Ullman–Goldberg coupling of 41b with Boc-hydrazine followed by deprotection and oxidation then affords 35 [55]. Asymmetric diazocines can be synthesised by Sonogashira cross-coupling

• bromide 47, followed by Fmoc protection of 56, Boc deprotection of 57, reduction of the NO2 group to NO and intramolecular Mills coupling to form 35h. Removal of the Fmoc protecting group under basic conditions affords the unsubstituted product 35d which, after N-alkylation or acylation affords the

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• amino alcohols derived from furfural and ʟ- or ᴅ-valinol were subjected to Torii-type ester electrosynthesis to obtain the corresponding unsaturated esters. These served as key intermediates to prepare (S)- and (R)-enantioenriched unsaturated amides by N-Alloc deprotection which induced concomitant

• ][24] (Scheme 1). The proposed strategy relied on the N-deprotection of the intermediate ester 3d inducing O-to-N rearrangement to form amide 5 as a precursor of vinyloxazoline 6. For this purpose, Alloc (allyloxycarbonyl) turned out to be a suitable N-protecting group as it was compatible with the

• electrolysis conditions and its removal was compatible with the double bond and acetal functions in ester 3d (see Supporting Information File 1 for attempts of other protecting groups such as Boc, Troc, and tfa). However, Pd-catalyzed N-Alloc deprotection induced isomerization of the double bond leading to the

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• -protected malassezione, which upon deprotection yields malassezione in an overall yield of ca. 20%. This is an improvement over the preparation of the isonitrile followed by an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction, which generated malassezione with an overall yield of ca

• advisable to stockpile the penultimate synthetic intermediate 23 and subsequently conduct the deprotection on the smaller scale. Conclusion Overall, we have developed a facile synthesis of the natural product malassezione, utilizing an EDC-mediated coupling of N-Boc-protected indole-3-acetic acid. The use

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• ]. For the synthesis of macrocycles M2 with two BINOL units, we relied on the monoiodide 12, which was first reacted in a two-fold Suzuki coupling to install the first linker, followed by silyl deprotection and introduction of the second linker via nucleophilic substitution [51]. Both procedures require

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• all Bz groups with 1 M NaOH (dioxane/MeOH/H2O, room temperature). The monophosphorylated trisaccharide 1 was obtained in 60% overall yield over two steps from 12 after purification over a SephadexTM LH-20 column. It was noted that the switch of deprotection sequences (first Bz groups, second Bn and

• over the following steps: 1) deprotection of the TBDPS group, 2) phosphitylation of the free alcohol with phosphoramidite 11 in the presence of 1H-tetrazole and 4 Å MS, and 3) oxidation of the phosphite by mCPBA. Hydrogenolysis of Bn and Cbz groups in 14 with Pd(OH)2/C and subsequent saponification of

• yield via the switch of the TBDPS group with the phosphate group. First global deprotection of Bn and Cbz groups in 18 with Pd(OH)2/C, followed by saponifications of all Bz groups with 1 M NaOH provided the desired monophosphorylated pentasaccharide 3 in 56% overall yield, which is the major glycan

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• the presence of chromium trioxide–3,5-dimethylpyrazole complex [41] to provide compound 17 in 76% yield. After deprotection of the TBS and TES groups with TBAF, brassicicene A (7) was obtained in 75% yield. Compound 17 was subjected to α-hydroxylation from the less-hindered convex face using Davis’s

• oxaziridine [25], furnishing intermediate 18 in 72% yield. After deprotection of the TBS and TES groups, brassicicene R (8) was obtained in 70% yield. Therefore, alterbrassicicene E (6) and brassicicenes A (7) and R (8) were synthesized from brassicicene I over 4 or 5 chemical steps. Conclusion In summary

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• and deprotection steps, functional group transformations, stereocontrolled allylation, cross-metathesis, and Horner–Wadsworth–Emmons (HWE) olefination. This method highlights the power of catalytic stereocontrol, achieving the complex architecture of borrelidin fragments with efficiency and precision

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• deprotection products, provides an interpretation of the NMR-spectra of (2R,6S)-9 in regard to conformation. This also offers insight into how specific constraints lead to certain conformations in six-membered rings, such as half-chair conformations. Noteworthy, the application of ᴅ-aminoadipic acid as an

• ) deprotection. Overview of reduction and deprotection to the final pipecolic acid derivatives (2R,6S)-5. Screened conditions for the Suzuki–Miyaura cross-coupling between bromide 2 and phenylboronic acid (8a). Overview of the relevant compounds with their chemical shifts δ, multiplicity, coupling constants J

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• followed by deprotection completed the total synthesis, giving rise to (−)-cephalocyclidin A in 10 steps from known compounds. Conclusion In summary, the perception of enamides as stable chemical entities with limited utilities in organic synthesis has evolved, and these compounds are now widely used in

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• and excellent yield of 94% (Scheme 1). A chemoselective deprotection of the mannosyl thioacetate 7 to yield the glycosyl thiol 8 was achieved using 0.95 equivalents of sodium carbonate. The crude product was in turn submitted to a Buchwald–Hartwig–Migita cross-coupling reaction [33] with the

• antenna 17 in 73% over two steps. Subsequent deacetylation quantitatively yielded 6αMan 4 (Scheme 2A). Finally, the third required glycoazobenzene antenna, the 3-(α-ᴅ-mannopyranosyl)mannoside 3αMan 5, was directly obtained from the known mannosyloxyazobenzene mannoside 18 [24] after Zemplén deprotection

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• peptide carbonyl group. Both moieties result from the glyoxylate compound (Scheme 43). There are many examples in which the ester moiety opens the possibility of a further intramolecular cyclization with a nucleophile (for example, a protected amine in an Ugi/deprotection/cyclization sequence [98][99][100

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• . Using diphenylamine as a more electron-rich amine resulted in the formation of diphenylamino-substituted N-acetyl diazocine 20 in a significantly lower yield of 25% starting from the bromide 2 and 47% starting from the iodo precursor 3 (Table 5). Deprotection of carbamate 19 with trifluoroacetic acid

• the switching behavior while weak +M substituents like bromine and fluorine as well as electron-poor heteroaromatic systems lead to increased thermal half-lives. An amino-substituted derivative 21 was obtained via Buchwald–Hartwig coupling with Boc-carbamate and subsequent deprotection. Amino

• of amino-N-acetyl diazocine by deprotection of the carbamate. Reaction conditions for the attempted Ullmann-type reaction with sodium azide. Reaction conditions for the palladium-catalyzed introduction of a nitrile functionality. Quantum yields of N-acetyl diazocine 1 in organic and aqueous media

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• glycoside 8 (Scheme 1). Glycosylation is considered as the most crucial step in any oligosaccharide synthesis, although it may be argued that, building block preparations or final deprotection steps remain equally demanding. The main challenge of glycosylation lies in the structural complexity of the

• , however, are used synonymously owing to their same participating property and the same Zemplén deprotection strategy [87]. A recent study showed the use of modified Zemplén conditions to synthesise deacetylated methyl β-glycopyranosides directly from per-O-acetylated α-glycosyl halides using a

• leading to lower amounts of orthoester side products. However, the removal of the pivalate group requires much harsher reaction conditions owing to its steric bulk. Hence, there has been much study to derivatise the pivalolyl ester necessitating milder deprotection conditions. Crimmins et al. in 1998

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• , followed by silyl deprotection and azide cycloaddition resulting in the triazole product. The presence of Cu(OTf)2 as the catalyst, sodium ascorbate as a mild reductant and TBAF to deprotect the alkyne moiety are crucial in the cycloaddition step. Conclusion In this review the developments on the

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• authors prepared a wide scope of axially chiral products 186 in high yields with excellent enantiomeric purity. The reaction allows lowering of the catalyst loading to 2 mol %. Deprotection of the amino group enabled subsequent transformations, such as a reaction with isocyanate from which a new potential

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• challenging, if not impossible. In order to overcome this problem, we opted to synthesize benzo[j]fluoranthene analogues with differentially protected oxygens so that specific positions can be functionalized further if needed after selective deprotection. To this end, first we accomplished an efficient

• via the deprotection of the -OTIPS silyl ether under the reaction conditions. A final MOM-deprotection under acidic conditions led to the formation of the desired benzo[j]fluoranthene 28 in 82% yield. Conclusion In conclusion, we have demonstrated the successful synthesis of heterocyclic fluoranthene

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• ). Firstly, hydrogenation with palladium on carbon led to the formation of 55 in a good yield. Secondly, an alkylation of the NH of the indole followed by intramolecular cyclization led to tetracyclic derivative 56 in an 80% yield. Next, a deprotection of the azo nitrogen atom led to derivative 57 in a 92

• formed N–N axis conducting to the origin of diastereoselectivity in the reaction. The treatment of 79 with base afforded the pyrrolinone 80 in 82% yield. On the other hand, the deprotection of derivative 78f led to the hydrazine 81 in an excellent yield. All the derivatizations occurred with the

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• synthesizing diverse scaffolds [6]. Furthermore, the Ugi reaction exhibits versatility in forming both fused and unfused heterocyclic compounds, involving 4-, 5-, 6-, and 7-membered rings [17]. This capability is exploited by various approaches, including the Ugi–Deprotection–Cyclization strategy (UDC) and

• ] developed artificial, ‘natural-like’ polyphenols, using the Ugi reaction, since it leads to mixed polyphenol–peptidomimetic structures (Scheme 4). The procedure involved an Ugi reaction using phenolic building blocks protected as allyl ethers, followed by deprotection, acetylation, and high-yielding

• years, the Ugi reaction has emerged as a highly considered reaction due to its mild conditions, broad applications, and product diversity. It enables the selective assembly of precursors, facilitating various post-reaction transformations such as deprotection cyclization, 1,3-dipolar cycloaddition, and

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

• steric demand of the isatin moiety and the α-anomeric form would result in a disfavorable 1,3-diaxial interaction between the isatin and the formyl group located at carbons C-1 and C-3, respectively. Deprotection with ammonia afforded the deprotected glucoside β-24a in anomerically pure form. Following

• of the 3-fluoroaniline moiety, presumably due to steric reasons. Deprotection of the isatin-N-glucosides 23b–f and xyloside 23g proceeded uneventfully and afforded products 24b–g in 50–85% yields. All products were isolated as the β-anomers. In our group, we also studied the synthesis of indirubin-N

• indirubin-N-glycosides Thioindirubin-N-glycososides In our group, we studied the reaction of isatin-N-glycoside 16a with thiaindan-3-one which afforded red colored thioindirubin-N-rhamnoside β-32a in very good yield and with excellent Z-selectivity (Scheme 20) [26]. Deprotection of β-32a afforded β-33a in

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

• synthesis, the deprotected derivatives such as 69 are desired for the synthesis of natural products. Therefore, an easy-to-perform two-step deprotection procedure was developed that is based on methylation of the phenolic hydroxy group with an excess of MeI in acetone at rt (68), followed by oxidative

• -morpholinyl amido and benzophenone imino groups with LiAlH4 and NaBH4 afforded the corresponding syn-2-benzyl-1,3-amino alcohol 134 in 83% yield. In the case of the dimethylamide derivative, deprotection of benzophenone imine 128 with NH2OH·HCl followed by the LiAlH4 reduction gave rise to chiral syn-2-benzyl

• N-(2-hydroxy)phenylimines with allyltributyltin. Scope of the reaction [37]. The two-step N-(2-hydroxy)phenyl group deprotection procedure [37]. Low-temperature (−40 °C) NMR experiments evidencing the reversible formation of the active COBI–imine chiral complex [37]. Highly chemoselective and

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• %. Silyl deprotection with (n-C4H9)4NF in THF followed by acetylenic oxidative dimerization under Hay conditions produced the desired DBA 5 in 12.7% yield. It should be noted that a thermodynamically more stable trimeric macrocycle was also formed in 17.7%, but it was not isolated and purified because it

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

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

• 11 are formed via Hantzsch's thiazole synthesis. After acidic deprotection to thiazolylhydrazines 12, these react with enolates of 2,4-diketoesters, which are intermediaries prepared in a separate reaction vessel, yielding the corresponding (thiazol-2-yl)pyrazoles 8. However, hydrazines are not

• (hetero)aryl iodides gives rise to 3-arylalkynyl acetals 142. Since 3-arylpropynals are sensitive to oligo- and polymerization, it proved useful to perform acetal deprotection and cyclization with hydrazine hydrate in a one-pot procedure to give 3-substituted pyrazoles 141 (Scheme 48) [151]. Given that