Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• [27]) and coupling partners [28], great attention has been paid to a stereoselective glycosylation by sterically fixed glycosyl fluorides as glycosyl donors [29][30][31]. The enhanced stability of glycosyl fluorides has also allowed to develop a straightforward protecting-group-free strategy towards

• through the neighboring ester type protecting group assistance. At lower temperatures the glycosylation yield was lower, although full conversion of glucosyl fluoride β-9 was still observed. Compared to the analogue mannose derivative α-1a, glucose β-9 turned out to be less stable and more prone to

• various side-reactions. A series of side-products formed by hydrolysis and protecting group migrations were detected and their structures are proposed (see Supporting Information File 1). Next, glycosyl fluorides α-11 and α-12 containing more acid-sensitive acetyl protecting groups were applied for the

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

• of NaHMDS in order to selectively alkylate the 2'-OH, followed by TBAF treatment to remove the MDPS protecting group. The 2'-O-MOE soon became the gold standard alkyl modification, owing to its improvement in therapeutically relevant properties. Compared to 2'-OMe RNA, the 2'-O-MOE RNA analogue has

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• -iodoaniline (12) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-[tris(1-methylethyl)silyl]-1H-pyrrole (13) according to Pratt’s conditions (Scheme 3) [29]. Subsequently, to remove the triisopropylsilyl (TIPS) protecting group, compound 14 was treated with tetra-n-butylammonium fluoride (TBAF) in THF

• prepared from an appropriate carboxylic acid through a Curtius rearrangement reaction (50–98% yield). Treatment of urea derivatives 19a–d with CBr4, PPh3, and Et3N afforded carbodiimides 20a–d in 64–75% yield. Compounds 21a–d were obtained in situ following the removal of the TIPS protecting group in 20a–d

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

• Discussion Synthesis of the GuNA[Me] phosphoramidites bearing either an A, G, or mC nucleobase The preparation of the GuNA[Me]-A, -G, and -mC phosphoramidites 3a–c needed for the synthesis of the GuNA[Me]-modified oligonucleotides is detailed in Scheme 1. The acetyl group was selected as a protecting group

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

• ). Enantiospecific synthesis of TKM-38 For the enantiospecific synthesis of TKM-38, which uniquely bears an eight-membered azacycle as the ring C, we explored 1) the amino-protecting group and 2) the conditions for the cyclization of the medium-sized ring by ring-closing metathesis (RCM). Finally, the established

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• structure [30]. These lipopeptides have a discrete molecular weight and are produced by Fmoc (fluorenylmethoxycarbonyl protecting group) SPPS, a procedure in which the peptide chain is assembled stepwise while attached to an insoluble resin support, which allows the easy removal of the byproducts at each

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• protecting group under acidic conditions was accompanied by cyclization in situ [14][15][34][35] and pyrrolizinone derivative 17 was obtained efficiently on a multigram scale over two steps. Originally, it was expected that adapting the conditions (NaH, RCOCl, THF) used for the acylation step in 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

• 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

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• studied computationally (Figure 2). To this end, a model substrate bearing p-toluensulfonyl as the protecting group on the nitrogen atom was chosen owing to the compatibility with such a process [16]. The structures were located using the B3LYP density functional theory method as implemented in the

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• adenosine [33][34]. The 3′,5′-O-di-tert-butylsilyl protecting group, in contrast to the Markiewicz group (1,1,3,3-tetraisopropyldisiloxane) can be selectively removed with HF-pyridine [35][36]. It was used for the iodination of cytosine residues previously [37], but to the best of our knowledge never for

• the iodination of a purine nucleobase, which is achieved under harsher conditions. Thus, the 3′,5′-O-di-tert-butylsilyl protecting group was introduced, followed by reaction of the 2’-OH group with TBDMS chloride to generate intermediate 10 (Scheme 2). Subsequently, the iodination was carried out

• migration of the TBDMS protecting group and consequently formation of the 3’-O-TBDMS isomer under Sonogashira conditions, which accounts for the reduced yield. This certainly can be counteracted by further reducing the reaction temperature of the Sonogashira coupling. Under the conditions applied here

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• . Cyclization to form the second pyrrole ring was achieved by selective Buchwald–Hartwig amination of dibromide 31 with n-propylamine to give TIPS-protected SN4'' 32 in 61% yield. Final removal of the TIPS-protecting group by TBAF gave the novel SN4''-system 33 in 98% yield (Scheme 6). All prepared S,N

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• was achieved with exclusive regioselectivity in peptides, with modest to moderate diastereomeric ratios of the fluorinated products (Scheme 29). With the optimum PSCat in hand, it was necessary to find a protecting group (PG) for the amine that would not undergo fluorination or oxidation when treated

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• treatment with 1 M HCl solution the Boc protecting group was split off (third step), and the desired NDI derivatives 3a and 3b were obtained in a yield of 39% and 44%, respectively. For the preparation of NDI 5, compound 1 was first monofunctionalized at the core with 2-dimethylaminoethylamine in a

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• nanostructures as well as the secondary structures. Results and Discussion Solid-phase peptide synthesis and purification The target octapeptide was synthesized in the solid phase following four steps, including: i) deprotection of the Fmoc protecting group, ii) coupling of an amino acid, iii) cleavage of the

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• removal of the silyl protecting group, followed by a carboxylation and acylation gave 13. Koide’s group [13] reported a second-generation route to 13, which utilized the Corey–Bakshi–Shibata chiral oxazaborolidine catalyst 21 [20] for the asymmetric reduction of the THP-protected 5-hydroxy-3-pentyn-2-one

• Kitahara’s synthesis [8][9], the Wittig olefination of 24, followed by a catalytic hydrogenation, removal of the dimethylaminal protecting group, and lactonization gave 25 as a mixture of diastereomers (Scheme 2). The further transformation of 25 afforded the dihydropyran 26, which upon catalytic

• metathesis using Grubbs’ 2nd generation catalyst (G-II, Scheme 3) [13]. Replacing the N-Boc protecting group with an N-tosyl group and allylic oxidation gave 30. The introduction of the allyl group at C-11 made use of the Kishi protocol [22] of the allyl-Grignard addition, followed by an ionic reduction. The

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• problematic synthesis of monophosphorylated mono- and disaccharide lipid X using a combination of established chemistry and a novel 2-naphthylmethyl ether (Nap) protecting group for “permanent” protection of hydroxy groups. Of particular note is the fact that the key Nap protecting group is able to remain in

• compound 13. Then, (2-naphthyl)methylene acetal [21] was used to protect the C-4,6-hydroxy groups using 2-naphthaldehyde dimethyl acetal and 0.2 equiv of camphorsulfonic acid (CSA). These protecting group manipulations resulted in the exposure of the C-3 hydroxy group in compound 14 for further acylation

• prepared from the common building block 15 through multiple protecting group manipulations (Scheme 2). The N-Troc group in 15 was removed by treatment with zinc in a mixture of acetic acid and CH2Cl2. The resulting amine 16 was protected immediately as fluorenylmethylenoxy (Fmoc) carbamate by reaction with

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• gave 11 in good yield. Likewise, 6-O-benzyl derivative 12 was prepared to reduce reaction steps and to ensure a clean progress of the benzyl protecting group removal by catalytic hydrogenation (Scheme 2). The direct thioglycosylation of 11 with ethanethiol in the presence of BF3∙OEt2 afforded 2-thio-ᴅ

• protecting group in derivative 14 led to alcohol 15 as the common intermediate for the synthesis of target structures 2a and 3a. The fully deprotected target compound 2a was obtained in good yield by acidic hydrolysis of the acetonide protecting group with 3 M HCl in THF followed by catalytic hydrogenation

• % and 54% yield, respectively. Moderate yields of 2-thio-ᴅ-tagatofuranosides 17 can be explained by cleavage of the benzyl protecting group [21] as well as further side reactions (Scheme 4). In order to increase the yield of 2-thio-ᴅ-tagatofuranosides 17, compound 12 was converted to the more reactive

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• excellent yields. Remarkably, a high functional group tolerance was observed, including heterocyclic substrates. In contrast, the N-substitution pattern clearly impacted the efficiency of the reaction. Indeed, exchanging the N-sulfonyl or N-acetyl protecting group with other functionalities, such as

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• reducing-end monosaccharide 14 equipped with the linker in 70% yield as a mixture of anomers (α:β = 2:1) (Scheme 2). The reductive opening of the benzylidene protecting group in 14 enabled the separation of anomers and furnished acceptor 15α [28], that was reacted with thioglucoside 11 to yield exclusively

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• diphenylphosphoryl azide (DPPA) in excellent yield. Finally, the oxazoline group, which acted as directing and protecting group, was removed in a three-step sequence of N-methylation, reduction of the in situ formed iminium ion and acidic hydrolysis. This afforded the azide-functionalized para-bromobenzaldehyde 3 in

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• cores for these compounds in high yields (63–83% over 3 steps) with no need for chromatography. Key to this transformation is the phosphoramidate protecting group, which is stable to metalation steps. Keywords: arginine; Horner–Wadsworth–Emmons; integrin; phosphoramidate; tetrahydronaphthyridine

• , exploiting the base stability of the phosphoramidate protecting group. A variety of bases were trialed at 0 °C for the initial N-phosphorylation, with 10 minutes allowed for complete deprotonation to occur (Table 1). Only minimal phosphorylation was observed when using potassium tert-butoxide (Table 1, entry

• phosphoramidate protecting group, which was superior to the more commonly applied Boc protecting group which was unstable to the lithiation. This synthetic route replaces traditional Wittig and tandem alkylation/reduction methodologies, which suffer from complications arising from troublesome byproducts and

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• conclusively to test for binding behavior and selectivity, both isomers a(CFC)2 and p(CFC)2 were synthesized using a suitable protecting group strategy (Scheme 2b). One of the Trt protection groups was replaced by an acetamidomethyl (Acm) group (CFC(Acm)), which is stable under the cleaving conditions of the

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• [3 + 2] methylenecyclopentane annulations of olefins with methylenecyclopropanes. This regioselective, mild, and protecting group-free annulation requires only an equimolar amount of the reacting alkene and does not require an excess of the reacting alkene, unlike other methods [9]. Furthermore, the

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• oxazolines in good yields (products 131a–e). Aliphatic oximes also enter this transformation, including an oxime containing a TBDPS protecting group (products 131f–h). The combination of AgSCF3 and catalytic amounts of Cu(OAc)2 was used for the synthesis of trifluoromethylthiolated isoxazolines 133 from

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• product 2-[18F]FPhe 46 in 43% yield, whereas under microwave irradiation a 34% yield was obtained. Under the optimized conditions, the enantiomeric purity was reported to be ≥94% ee [46] (Scheme 10). 1.3. Photooxidative cyanation of fluorinated benzylamine A convenient, protecting group-free, and

• the primary hydroxy group (Alloc) gave alcohol 117 in good yield. The fluorination of 117 was achieved by treatment with DAST to form 118. Then, selective removal of the Alloc protecting group using Pd(PPh3)4, was followed by oxidation of the resulting Boc-protected amino alcohol 119 to give the N-Boc

• group for the reaction providing the desired product with 57% yield. Also, methyl and ethyl esters as C-terminal protecting groups in combination with phthalimino as the N-terminal protecting group, were both successfully explored. However, when the trifluoroacetyl amide was used as a substrate the