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

• a robust protecting group and to conduct final deprotection under neutral conditions. After initial experimentation with benzyl glycosides (Scheme 1, PG = OBn), phenyl thioglycosides (Scheme 1, PG = SPh), readily available from 1,6-anhydropyranoses [39] as we described earlier [40] were found to

• -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

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• kinetics and higher solubility in organic solvents, useful for automated synthesis, such as the Beaucage reagent [86]. Conveniently, during deprotection of the support-bound oligonucleotide, aminolysis removes the β-thiobenzoylethyl group from the backbone to generate the free PS2-modified oligonucleotide

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• deprotection was achieved via 20% piperidine in DMF (1 × 2 min and 1 × 18 min) to prepare the resin for the next coupling step. The resin was washed three times with each solvent in the given order DMF, DCM, and DMF after every reaction step. Peptide sequences T7: H-HAIYPRH-NH2 Modified T7: dipalmitoyl-Dap

• . Coupling of Fmoc-Dap(Fmoc)-OH and Fmoc deprotection were carried out as described above. To ensure the complete lipidation of the two free amines of Dap, 8 equiv of palmitic acid, 8 equiv of HATU, and 12 equiv of DIPEA in DMF were used. Cleavage of the peptide–lipid conjugates from the solid support and

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

• deprotection was achieved by using trifluoroacetic acid (TFA) before the preparative HPLC. The synthesis of compounds A22 and A23 was accomplished by an alternative route elaborated in Scheme 5. Coupling of compound 5 and intermediate 2 was achieved by using HATU and DIPEA in a DMF/CH2Cl2 mixture to form the

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• cyclized radicals 22 couple subsequently with TEMPO providing lactams 12a–k after deprotection of the TMS groups. The cyclized tertiary alkoxyamines (R3 = Me) are known to be thermally labile [89][90][91][92] and consequently 4-isopropenylpyrrolidones 12g,k are isolated as the exclusive products. The

• α-(aminoxy)amides 9. Thermal radical cyclization of compounds 9 and further deprotection (general procedure) The α-(aminoxy)amide 9 (0.65 mmol) was heated in t-BuOH (6 mL) in a microwave reactor at 150 °C for 1 h. The reaction mixture was diluted with diethyl ether (5 mL), transferred into a round

Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

• Naohiro Horie,
• Takao Yamaguchi,
• Shinji Kumagai and
• Satoshi Obika

Beilstein J. Org. Chem. 2021, 17, 622–629, doi:10.3762/bjoc.17.54

• attention to the reactivity of each nucleobase. Finally, the acetyl group was successfully removed by extending the deprotection time to 10 h. The yield range of the designed oligonucleotides ON1–ON3 was 12–25%, as shown in Table 1. Duplex-forming ability of oligonucleotides modified with GuNA[Me]-A, -G, or

• treated with a 1:1 mixture of 7 N ammonia solution in methanol and 40% aq. methylamine at room temperature for 10 h to remove the solid support, and then the mixture was heated at 60 °C for 10 h (mC) or 15 h (A and G). After deprotection, the oligonucleotides were rapidly purified using a Sep-Pac® Plus

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• and Figure 2, were unambiguously determined later from crystallographic and spectroscopic studies of the 2R-derivative 9 (see below). Scheme 3 shows the synthesis of the (2R)-enantiomer of MC-27, 4. The deprotection of the PMB group of 9 (tR 11.5 min in Figure 2) by CAN proceeded smoothly at rt to

• only a monocarboxylic acid product, and the menthyl ester remained unaffected (structure not shown). Fortunately, the complete deprotection of the two esters was cleanly possible under acidic conditions (6 M aq HCl, 1,4-dioxane, 75 °C, 4 days) to furnish (2R)-MC-27 (4) in 48% yield (Scheme 3), the

• ], which gratifyingly furnished (2S)-TKM-38 (3*) in a good yield (77%) after ion-exchange chromatography (Dowex® 50W x8-200, H+ form). LiOH, which was used for the final deprotection in the synthesis of the MC-27 enantiomers 4 and 4* (see Scheme 3 and Scheme 4), was not capable of facilitating the removal

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• derivative. Such nitrogen protection/deprotection (e.g., acetylation/deacetylation) is often used in the other synthetic strategies described in Scheme 1. Therefore, the starting isatin was acetylated first with acetic anhydride [47] in 95% yield and then reduced with various complex borohydrides (e.g

• with inversed configuration of the double bond. Several synthetic strategies starting from isocyanate [22][23] or oxindole [4][12] precursors work well only with protected nitrogen(s) in the starting compounds whose preparation and protection/deprotection also lengthens the total synthesis and

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

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

• converted into N-Cbz-1-aminoalkylphosphonochloridates 13, which were further coupled with methyl (S)-2-hydroxy-4-methylpentanoate (14), affording the protected phosphonodepsidipeptides 15. Finally, after deprotection the free phosphonodepsidipeptides 10 were obtained [19]. The disodium salts of the trans

• amino acids 206 to give the corresponding protected phosphonopeptides 207. After deprotection by hydrogenolysis and treatment with CF3CO2H, the phosphonodepsipeptides 208 were obtained (Scheme 38) [59]. Phosphonodepsipeptides with C-1-hydroxyalkylphosphonic acids are also accessible through carbene

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• chromogenic 5-O-feruloylated α-ʟ-arabinofuranosides 1a and 1b is usually achieved using a multistep pathway that involves trapping the furanose conformation, anomeric activation, glycosidation, regioselective deprotection of the primary hydroxy group, feruloylation, and final deprotection to yield the target

• the primary hydroxy group compare favorably with the previously reported overall yield (46 and 47%, respectively, in three steps) [15][16][17][29], which relate to the selective enzymatic O-5-deacetylation and esterification of the primary hydroxy group and a final deprotection of the 2,3-O-acetyl

• groups of the glycoside and the O-acetyl group of the ferulate moiety. The fact that lipase-catalyzed transesterification obviates the need for protection and deprotection is a considerable advantage because the final deprotection in the chemical pathway is complicated by the presence of another ester

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• been used in a 1.2-fold excess) turned out to be very laborious. Moreover, the subsequent deprotection to the natural product 1 could not be achieved sufficiently: After treatment of 10a with tetrabutylammonium fluoride (TBAF), the signals of 1 could be detected in a 1H NMR spectrum of the crude

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• proceed stereoselectively when organolithium compounds were added to 2,3-diphenyl-2H-azirine. This is a fast, safe, green and convenient method to access this interesting structural motif without requiring protection/deprotection steps or long synthetic pathways. Flow generation and transformation of 2H

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• chiral mono-Boc-1,2-diamines and (dialkyl)malonyl dichloride via open diamide-bis(N-Boc-amino) intermediates (65–91%). Deprotection and ring closure with a second malonyl unit afforded the cyclam tetraamide precursors (80–95%). The new protocol allowed the preparation of the target cyclam derivatives (53

• reaction of the mono-Boc-protected diamine (A-Boc) followed by Boc deprotection with HCl, and final ring closure of diamide–diamine intermediate 1a with a second malonyl unit to give tetraamide product 2a (Scheme 1a). The equivalent ethyl-substituted cyclam 4a was prepared in comparable yield (63% over the

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• library building block acid chloride 2. The libraries were prepared in a 3-step manner: 1) amide coupling; 2) deprotection of the 2-methoxypyridine through hydrolysis at elevated temperatures; and 3) the final SNAr or Ullman step to introduce the amine vector with variable yields and chromatographic

• to purify the Boc protected intermediates 9a–e by Prep-LC–MS as the final products 10a–e were difficult to purify owing to their particularly poor solubility in the mobile phase. The final products were delivered as their HCl salts following Boc deprotection using HCl in dioxane overnight

• under these acidic conditions, hydrolysis of our py–OAt ether 15 would be accompanied by in situ deprotection of the Boc group to afford directly our final pyridin-2-(1H)-one products 16 and thereby eliminating a purification stage compared to the previous route. As literature was scarce for this

Supramolecular polymers with reversed viscosity/temperature profile for application in motor oils

• Jan-Erik Ostwaldt,
• Christoph Hirschhäuser,
• Stefan K. Maier,
• Carsten Schmuck and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2021, 17, 105–114, doi:10.3762/bjoc.17.11

• cyclisation. Thus, all compounds feature a central BINAM unit, which is connected to the BUs (GCP or ACP) via a propionamide linker [29]. The synthesis of compound 1 was carried out starting from BINAM by coupling with GCP derivate 5 [12][13] after activation with thionyl chloride (see Figure 3). Deprotection

• with TFA yielded the bis-GCP derivate 1 in 40% yield over two steps. Accordingly, the ACP derivative 6 was coupled with BINAM, followed by deprotection to give bis-ACP derivative 2 (60% yield over two steps). For the extension of the linker unit, BINAM was first coupled with glutamic acid (O-benzyl and

• N-Boc protected). Removal of the Boc groups, coupling with the ACP precursor 6 and final deprotection gave the extended bis-ACP compound 3 (44% yield over 4 steps). Finally, BINAM was first brominated in the 6-position to give 8 [30], followed by coupling with the ACP precursor 6. This allowed the

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• -mediated amidation of Boc-protected tri-ʟ-phenylalanine, as β-sheet directing peptide sequence, afforded the peptide amphiphile in good yields. After deprotection of the N-terminus with TFA, molecule 4 was suitable for coupling to the branching unit to obtain the desired dendritic peptide amphiphiles. In

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• %). Deprotection of the TBDMS ether of stannane 40 with tetra-n-butylammonium fluoride (TBAF) in THF and then subsequent Swern oxidation of the crude alcohol gave aldehyde 41 in 71% yield. The aldehyde 41 was treated with ethyl isobutyrate (42) in the presence of LDA to afford the aldol adduct (Z)-(rac)-43 in the

• diastereoisomers. Then, the key aldol reaction of 123 with silyl enol ether 53 under optimized Mukaiyama–Kiyooka conditions, followed by TIPS deprotection, afforded adduct (3R)-(+)-11 in 63% yield and with 94% ee. Ester hydrolysis followed by acetylation of (3R)- (+)-11 produced acid derivative (+)-76 [50] in 87

• ). Initially, (E)-pent-2-en-4-yn-1-ol (124) was smoothly converted into the desired bromide derivative 125 [67] in two simple steps. The bromide 125 was then reacted with pre-lithiated oxazole derivative 120 [68][69] under optimized conditions to produce coupled product 126. The selective deprotection of the

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

• dipolar cycloaddition to produce tricyclic isoxazolidines [40]. The synthesis started from 5-hexyn-1-ol (4, Scheme 2). The alcohol was treated with dihydropyran followed by alkylation using butyllithium and then, acetal deprotection, providing the alcohol 5 as a key starting compound for the (±)-adaline

• providing a mixture of monoprotected diols (−)-53 and 54 in a 10:1 ratio for the least sterically hindered alcohol in 98% yield. After chromatographic separation, (−)-53 underwent radical-induced Barton–McCombie deoxygenation (AIBN, Bu3SnH) to form (−)-55 in 82% yield. The double deprotection of (−)-55

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• and Mo catalysts. Beneficial effect of ethene atmosphere. Enantioselective dienyne metathesis [21]. Diastereoselective endiyne metathesis [31]. Synthesis of hepta-1,6-diyn-4-ol (4a). Protection of hepta-1,6-diyn-4-ol (4a). Alkylation of the protected diynols 7a and 8a. Deprotection of protected

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• nanoparticle surface after immobilization. Compound 2 was prepared by starting from potassium phthalimide and 1,12-dibromododecane (Scheme 2). The product resulting from this step was treated with bis(2-pyridylmethyl)amine to give a DPA derivative that was coupled to (R)-lipoic acid after deprotection to

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• moiety throughout (Scheme 3). Thus, the α,β-unsaturated ester 15 [25] was carried through a similar sequence to that previously described, i.e., dihydroxylation, cyclic sulfate formation, ring-opening with TBAF (although note the regioselectivity [31]), deoxyfluorination, and deprotection to deliver the

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• sodium cations requires further studies. Despite the unusual mass spectrometric behavior of the compound, the combined spectroscopic evidence strongly supports the identity of TBTQ-(OAcG)6. After deprotection of the glucose units, the acetyl signals disappeared in the 1H and 13C NMR spectra of the target

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• atmosphere. Then, water (100 mL) was added and the yellow precipitate was filtered, and washed with ether. After Boc and Fmoc deprotection by using TFA and piperidine, respectively, crude compound 4 was obtained. The crude product was further purified by column chromatography (1% methanol in chloroform