Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• perform equally well using conventional heating methods. Aniline 10 and carboxylic acid 13 were combined under standard (HBTU) amide coupling conditions to afford benzyl ester 14 in 52% yield. Compound 14 was subsequently debenzylated via hydrogenolysis to afford the target Db2 monomer 15 in 77% yield

• -nitroaniline into benzyl acrylate to afford compound 17 in 57% yield (Scheme 3). Aniline 17 then was subjected to a three-step Boc protection, nitro reduction, and coupling with isoorotic acid derivative 6 that afforded 18 in 39% yield over 3 steps. The benzyl ester was then cleaved under hydrogenolysis

• conditions to afford carboxylic acid 19 in 65% yield, followed by coupling with the PNA benzyl backbone 12 [38] to provide ester 20 in 54% yield. The final Db3 monomer 21 was obtained in 90% yield through benzyl cleavage using the standard hydrogenolysis conditions, similar to previous monomers. PNA

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• groups through hydrogenolysis, neutralization with cyclohexylamine and treatment with ion-exchange resin led to dihydroxyacetone phosphate. This 4-step method was more efficient than the previously reported dismutation of fructose-1,6-diphosphate [84] and 3-chloro-1,3-propanediol [85] which required more

• 2021, Wang reported the high efficiency of the non-precious bimetallic catalyst Ni–Mn in the selective hydrogenolysis of levulinic acid to 2-butanol in 82.5% yield under 5 MPa H2 at 240 °C (Scheme 76) [241]. The high basicity of the Ni–Mn catalyst results in a good affinity with the C=O or COOH groups

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

• ) and dissolved in ethanol (3 mL). A catalytic amount of Pd/C was then added and hydrogenolysis was conducted for 4 h with stirring under an H2-filled balloon. The reaction was monitored by TLC and, after completion of the reaction, the mixture was filtered through Celite, followed by washing of the

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

• of polar groups, including phosphoryl acid and amine groups [62]. After several optimizations, the following sequence was adopted to remove all Bn, Bz, and Cbz groups: 1) global hydrogenolysis of Bn and Cbz groups in 12 with Pd(OH)2/C in a mixed solvent (THF/MeOH/AcOH/H2O) and 2) saponification of

• 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

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

• -kilogram synthesis of PF-06878031 which is a key structural fragment of various GLP-1 receptor agonists [75]. As depicted in Scheme 28, the treatment of enantiomerically pure O-benzylglycidol (111) with ylide 105 generated from Me3SOI followed by hydrogenolysis and sulphonylation delivered oxetane tosylate

• benzotriazole-adduct formation proceeds poorly with sterically demanding secondary amines and fails with primary amines. However, the latter may be overcome by adding a temporary benzyl group on the amine which can be subsequently cleaved by hydrogenolysis as demonstrated by the authors. Finally, it was shown

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• under Pd-catalyzed hydrogenolysis afforded diamino acid ester 14 (75% yield) that was likely formed by ring-opening of the unstable N-unprotected 2-aminoproline followed by the reduction of the open-chain imine tautomer. Likewise, the open-chain amino alcohol 15 was formed also upon the reduction of the

• ester moiety with LiBH4. In the meantime, the hydrogenolysis of the benzyl ester in dipeptide 16 proceeded smoothly and afforded carboxylic acid 17 in 81% yield (Scheme 4) [16]. Conclusion In summary, the developed electrochemical decarboxylative amidation of readily accessible malonic acid monoesters

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

• described in the literature (Scheme 5) [41][42]. Treatment of a 3:1 mixture of the anti/syn-diastereoisomers of compound 3 with 1,3-propane dithiol in the presence of a small amount of scandium triflate [43] afforded compound 18, which was used in the next step without further purification. Hydrogenolysis

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• succeeded by the usual hydrogenolysis to furnish the carboxylic acid anti,syn-8a in 79% isolated yield and the lactone anti,syn-7b was recovered in 13% yield (Scheme 4) which was considered to be the reflection of the original composition of anti,syn-7a and -7b. The relative stereochemistry of anti,syn-8a

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• converted into the corresponding acids 4a,b by hydrogenolysis under mild conditions, which proceeded in quantitative yields (Scheme 4). It should be noted that this method of preparing β-lactam acids compares favorably with the alkaline hydrolysis of their methyl and ethyl esters, which does not always give

• ; reaction scale – 0.25 mmol; ascaled-up (1.5 mmol) yield. Negative results with several N-, O-, and C-nucleophiles and with diazo reagent 1m. Preparation of acids 4 by hydrogenolysis of benzyl esters and examples of acid 4a amidation. Supporting Information Deposition Number CCDC 2323689 (for 3t) contains

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

• conducted via catalytic hydrogenolysis, resulting in the formation of enaminoketones 32. Finally, enaminoketones were subjected to acid hydrolysis conditions facilitating ring closure and producing the spiro-2H-furan-3-ones 33 in moderate yield (Scheme 10). This procedure was also applied to norethisterone

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• ]methylphosphonate (10). The following hydrogenolysis under H2/Pd/C conditions in ethanol, afforded the desired diethyl (4-hydroxyphenyl)methylphosphonate (7), in an overall yield of 80%. The synthesis of diethyl [hydroxy(4-hydroxyphenyl)methyl]phosphonate (11) [55] started with the reaction of 4-hydroxybenzaldehyde

• ). Compound 15 reacted with diethyl phosphonate in the presence of a strong base (sodium methoxide) to afford diethyl [hydroxy(4-nitrophenyl)methyl]phosphonate (16) in 81% yield (Scheme 4). The hydrogenolysis of this compound under H2 on Pd/C afforded quantitatively diethyl [hydroxy(4-aminophenyl)methyl

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• . Finally, the benzyl-protecting groups in compound 7 were cleaved via hydrogenolysis, followed by co-evaporation of the resulting crude product in pyridine. This yielded a monopyridyl salt, setting the stage for the final lipid coupling and deprotection sequence. To establish the vital lipid diphosphate

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• transformation into divalent carbohydrate mimetics turned out to be a difficult task. We started the experiments with the hydrogenolysis of bicyclic 1,2-oxazin-4-ol 19 as simple model compound (Scheme 7). A methanol solution of 19 under an atmosphere of hydrogen was stirred for 17 h in the presence of palladium

• quantitatively available by sodium borohydride reduction of 7, we encountered the first problems. Under similar conditions of the hydrogenolysis the expected product 24 could be isolated as major component and characterized (Scheme 7, reaction 2), but the obtained sample contained unknown byproducts. It is

• other triazolyl-substituted aminopyran derivatives we encountered similar selectivity problems due to the sensitivity of benzylic bonds to the applied hydrogenolysis conditions [59]. Despite of the discouraging results with model compound 23 we nevertheless examined the reductive cleavage of bis(1,2,3

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

• derivative 2.6. The treatment of 2.6 with trimethylamine produced an ammonium salt. A treatment with silver carbonate was applied to remove any traces of bromide salts. Then, the secondary alcohol was deprotected by hydrogenolysis to produce 2.7 (lyso-PAF). Finally, the acetylation of the secondary alcohol

• the alcoholate reacted with 1-iodohexadecane to produce 3.3 in 50% yield. The phosphocholine moiety was incorporated by using 2-bromoethyl dichlorophosphate as a key reagent and following a previously reported sequence [67]. The debenzylation by using hydrogenolysis conditions produced 3.5 in 75% to

• hydrogenolysis to produce 1-O-octadecyl-sn-glycerol (4.10). It must be noted that the authors, after the deprotection of the two alcohol functions of 4.7, attempted the direct alkylation of the primary alcohol with octadecyltosylate. However, a mixture of mono and dialkylation was formed and were separated by

CO₂ complexation with cyclodextrins

• Cecilie Høgfeldt Jessen,
• Jesper Bendix,
• Theis Brock Nannestad,
• Heloisa Bordallo,
• Martin Jæger Pedersen,
• Christian Marcus Pedersen and
• Mikael Bols

Beilstein J. Org. Chem. 2023, 19, 1021–1027, doi:10.3762/bjoc.19.78

• compounds were made by tosylation of the corresponding partially benzylated cyclodextrins, hydrogenolysis and base treatment (see Supporting Information File 1 for experimental details). Compounds 5 and 6 have previously been made by direct tosylation of α-cyclodextrin which is a shorter route [17]. However

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• , photocleavage, hydrogenolysis of the remaining PGs, and purification (Figure 2C). The latter is commonly employed for compounds synthesized on L2 because of the poor stability of free-reducing glycans in basic conditions needed for the methanolysis step [33]. The isolated yields of the fully protected compound

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• -azaphosphocin-1(4H)-yl)acetate (4), respectively, in the presence of the Grubbs first generation catalyst via ring closing metathesis. The products 3 and 4 were further transformed to antitumor agents 5, 6, 9 and 10 through aminolysis with O-TMS hydroxylamine or hydrogenolysis followed by aminolysis with O-TMS

• -hexahydro-1,2-oxaphosphecine 2-oxide 26 in 70% yield. After the Pd-catalyzed hydrogenolysis, it was transformed to both cyclic ten-membered phostone 2-(4-methylphenyl)benzothiophene-fused 2-hydroxy-1,2-oxaphosphecane 2-oxide (27) in 40% yield and acyclic (4-(3-methyl-2-(4-methylphenyl)benzo[b]thiophen-4-yl

• )butyl)phosphonic acid (28) in 45% yield as a byproduct, which was generated from the Pd-catalyzed arylmethylic cleavage under hydrogenolysis conditions (Scheme 5) [22]. To avoid the formation of the acyclic byproduct, the same research group designed a new inhibitor with a reverse phosphonate bond

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• provided the seco-acid 75. Employing the same Mitsunobu conditions previously described [35], the authors were able to obtain the macrolide 76 in 81% yield which was then subjected to deprotection to give compound 77 (Scheme 14). The synthesis of 2 from compound 77 was achieved after hydrogenolysis of the

• benzyl ether. Further double bond formation in compound 78 employing triiodoimidazole and PPh3 led to 2 (route A, 32% overall yield from 52). The synthesis of combretastatin D-1 (1) was achieved from the cyclodehydration of compound 77, followed by the hydrogenolysis of the benzyl ether 79 (route B

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• in two steps from known ʟ-ribitol 1 [34] in good overall yield. Next, it was converted to the C-5 deoxygenated N-benzylpyrrolidine 6 via trityl ether cleavage, tosylation of the deprotected OH group, and reduction of the tosylate 5. Hydrogenolysis of the N-benzyl group in 6 followed by a removal of

• after hydrogenolysis and treatment with conc. HCl gave hydrochloride 10 (Scheme 1). The versatile intermediate 3 was further employed in the synthesis of the target compounds 17–20 (Scheme 2) homologated at the C-5 position. The transformation of pyrrolidine 3 to 13 included the replacement of the N

• -benzyl group with the Cbz group, trityl ether hydrolysis, oxidation of the liberated OH group, and stereoselective addition of MeMgBr to the resulting aldehyde functionality. Hydrogenolysis of the Cbz protecting group in 13 followed by N-alkylation afforded pyrrolidines 14–16 which after acidic

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• . These methods are so useful because virtually any chemical modification at the deprotected sites can be made followed by global deprotection of the O-benzyl groups with hydrogenolysis. Recently, we observed a strong substituent effect when substituted benzyl groups were used in these reactions with

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• shown in Scheme 2b and c. To access mixed oxime-hydrazone 5a, benzylamine was reacted with two equivalents of α-chlorohydrazone 9c to give bishydrazone 10, which was debenzylated by hydrogenolysis with Pd–C catalyst. The subsequent introduction of the oximinoalkyl unit was selectively achieved by

• . Hydrazinium dihydrochloride was isolated in some cases (confirmed by X-ray, mp, and FT-IR data) demonstrating the degradation of the heteroadamantane cage. Deprotection of Cbz derivatives by hydrogenation over Pd–C was more productive. Thus, hydrogenolysis of product 8b delivered the 1N,2O-TAAD derivative 15

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• diffuse intermolecular C–H···O contacts involving the phosphate and acetyl oxygen atoms. Deprotection of 16 was completed in two steps, first using hydrogenolysis with Adam’s catalyst (PtO2), followed by removal of the acetate protecting groups with Et3N/H2O/MeOH, and furnished the target glycosyl 1

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines

• Irina Fiodorova,
• Tomas Serevičius,
• Rokas Skaisgiris,
• Saulius Juršėnas and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 497–507, doi:10.3762/bjoc.18.52

• with 3,6-di-tert-butylcarbazole according to the procedure reported by us previously [29]. In order to remove the methylthio group in tCbz-mPYR and to obtain the 2-unsubstituted pyrimidine derivative 1, a hydrogenolysis reaction employing Raney Ni was carried out. Efficient methods for the introduction

• pyrimidine–carbazole TADF emitters bearing different substituents in position 2 of the pyrimidine moiety were successfully prepared by using Liebeskind–Srogl cross-coupling, hydrogenolysis, oxidation reactions of 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methyl-2-methylthiopyrimidine and following

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• and the benzyl groups were removed by hydrogenolysis using 10% Pd(OH)2/C in methanol at ambient temperature with a H2 balloon, which afforded the target trisaccharide 1 in 68% yield over three steps (Scheme 6). The structure of 1 was confirmed by several NMR spectroscopic techniques such as 1H NMR

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• hydrogenolysis conditions led only to the formation of several undesired byproducts. To our satisfaction when compound 12 was subjected to catalytic hydrogenation using Pd(OH)2/C in methanol [39], 2 was formed in 71% yield. Finally, (±)-codonopsinol B (1) was directly obtained from 12 in the yield of 58% (over