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

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• could be converted into N-acetates upon reduction with tributyltin hydride and azobisisobutyronitrile (AIBN), and the N-Cbz groups were removed to liberate the free amino groups during hydrogenolysis over Pd/C [259]. A collection of well-defined COS with defined DP and PA was prepared by AGA [93][157

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• % and exclusively β-selective [11]. Isomeric separation of this complex mixture was not completed at this stage and the material was next deprotected using hydrogenolysis to remove the benzyl groups. This furnished 20 in excellent yield (96%) as a 3:1 α/β mixture (δ 100.5 ppm [1JC1-H1 = 172 Hz, for the

• α-anomer]). Additionally, glycosylation of dibenzyl phosphate using the mixture 18/19 was successful and furnished the expected mixture of tetrazole N-regioisomers in 72% yield. These materials were not separated and instead exposed to hydrogenolysis conditions to deliver free ᴅ-manno C6-tetrazole 1

One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)

• Louis G. Mueller,
• Allen Chao,
• Embarek AlWedi and
• Fraser F. Fleming

Beilstein J. Org. Chem. 2021, 17, 1499–1502, doi:10.3762/bjoc.17.106

• to substituted imidazoles. Raney nickel hydrogenolysis was effective in interchanging the C4 anisylsulfanyl group for hydrogen (Scheme 3); attempted lithium–anisylsulfanyl exchange [19] or palladium- [22] or nickel- [23] anisylsulfanyl cross coupling was not successful. Raney nickel reduction of 7f

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• with either uracil or N6-benzoyladenine via Vorbrüggen’s method of nucleobase coupling to produce the double-headed nucleosides 85 and 86. Catalytic hydrogenolysis of the iodinated double-headed nucleoside 85 gave the nucleoside 87 (Scheme 19) [59]. Horton and Tsai [13] synthesized double-headed

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• -catalyzed hydrogenolysis in ethanol/acetic anhydride appeared to be a logical deprotection step [26], the desired fluoro sugars were contaminated with varying quantities of unidentified byproducts. However, clean debenzylation was achieved by first converting the azide to an acetamide on reaction with

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• -dimethylaminopyridine (DMAP) as the base. Then, the palladium-catalyzed hydrogenation of compounds B1–21 in THF or EtOAc led to the hydroxy derivatives C1–21. It has been observed that a catalytic amount of triethylamine (TEA) in EtOAc enhances the rate of the hydrogenolysis of benzyl ethers. Compounds C1–21 were then

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• (a solvent is the reagent and solvolyses include hydrolysis, glycolysis, alcoholysis and aminolysis) and hydrogenolysis reactions (H2 as reagent). Hydrolysis (sometimes called hydrocracking) is in between thermochemical and chemolytic processing, basically consisting of depolymerisation by the

• conditions. For instance, for polyesters, alcoholysis may provide mixed monomers formally derived from transesterification reactions [89][90], while aminolysis provides amides and alcohols [91][92]. In the search of “greener” technologies for plastic recycling, catalytic hydrogenolysis processes have been

• ), bis(2-hydroxyethyl)terephthalate (BHET), terephthalamides (TPM [171]) and EG (Figure 3). Catalytic hydrogenolysis, hydrolysis, methanolysis and glycolysis reactions of (postconsumer) PET have been reviewed, each showing their own advantages and disadvantages [172][173]. For instance, glycolysis

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• 17 was synthesized via the coupling of methyl N-Cbz-1-aminoethylphosphonochloridate (13b) generated from phosphonic monomethyl ester 12b and methyl (S)-2-hydroxy-3-phenylpropanoate (18) followed by hydrogenolysis. It was further coupled to cyclen to afford various cyclen-containing

• methyl N-Cbz-protected 1-aminoethylphosphonochloridate 13b with methyl ᴅ-lactate (22a) and methyl mercaptoacetate (22b), respectively, followed by a basic hydrolysis and hydrogenolysis. The bioassay results indicated that the phosphonothiodepsidipeptide 20b did not inhibit VanX (Scheme 3) [21]. It was

• -aminoethylphosphonochloridate (13b) with different benzyl 1-hydroxyalkanoates 26 followed by hydrogenolysis and hydrolysis. The bioassay results indicated that six out of the seven synthetic phosphonodepsipeptides 25 inhibited VanX with IC50 values ranging from 0.48 to 8.21 mM (Scheme 4) [7]. Two optically active

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• hydrogenolysis of benzyl ethers (H2, Pd) [72], DIBAL-H reduction of esters to form alcohols [73], oxidative cleavage of vinyl groups to form carboxylic acids (KMnO4) [74], and the conversion of the acids into amines using the Curtius rearrangement (SOCl2, followed by Me3SiN3, thermolysis, and acid hydrolysis of

• -difluorocyclopropanes in the synthesis of fluoroalkenyl-substituted compounds (monofluoroalkenes) have been actively studied. Great opportunities exist for the use of transition metal catalysis. The catalytic hydrogenolysis of 1,1-difluoro-3-methyl-2-phenylcyclopropane (151) led to the regioselective C2–C3 distal bond

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• , it was transformed into (E)-vinylboronate (+)-145b in perfect stereoselectivity by using the recently developed boron-Wittig reaction with bis[(pinacolato)boryl]methane (144) [79]. By applying the Corey–Fuchs dibromoolefination and followed by Pd-catalyzed hydrogenolysis under Uenishi's conditions

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• subjected to simultaneous catalytic hydrogenation and hydrogenolysis of the protecting group Cbz to give (−)-adaline (1) in 90% yield. The asymmetric synthesis achieved by Liebeskind et al. presented a high enantiomeric excess and good yields. Also, the proposed route differed from the previously mentioned