Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• rather hard to just reduce only one site in the presence of the others. Protecting groups are widely used to prevent reaction of one or more functional groups and let others to react [55][56][57]. Generally, protecting groups are covalently connected to the targeted groups, which requires

• prefunctionalization and deprotection synthetic procedures. Based on the logical concept of protecting groups, noncovalent interactions can be considered, because they can be built up in situ and are weak enough to let the substrate dissociate from the “protecting template” easily, omitting the complicated

• prefunctionalization and deprotection processes. Moreover, functional groups that are not suitable for being functionalized with protecting groups can also be incorporated into the noncovalent protective systems. Actually, the molecular container has been applied to work as a noncovalent protective module. In this

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• chirality transfer. With this positive results in hand, we incorporated 5 into the desired tetrapeptide 8. So far, we carried out peptide Claisen rearrangements only with small dipeptides, but never used longer peptide chains, such as tetrapeptides. We knew from previous work that the protecting groups on

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• because of the longer time needed. Next, we screened different protecting groups for the oxindole. Previously, Boc-protected oxindole 2a gave us the product in 75% yield, in dr 2.6:1 and in ee 90%/94% (Scheme 1, 3a). With a Cbz-protecting group the enantioselectivity decreased to 82%/88% (Scheme 1, 3b

• -protecting groups. Reaction conditions: 0.2 M solution of 1 (1 equiv), 2 (1 equiv), of catalyst D (0.1 equiv), chloroform, at room temperature; isolated yields after column chromatography; ee determined by chiral HPLC. Scope of the reaction (the relative configuration of the major diastereoisomer is depicted

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• , 1 h. In panel C), amino acids in R1 and R2 are with protecting groups and R2 is resin-bound (Rink amide resin); R3 = 4-phenylboronic acid or (4-ethylphenyl)boronic acid (P2–P5). Supporting Information Supporting Information File 6: Details on the amino acid and peptide synthesis, analytical data of

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• under basic conditions. (2) The protecting group is stable under the basic Williamson ether formation conditions. For this reason, we screened several potentially useful protecting groups against these two criteria using compounds 3a–l (Scheme 2). For criterion (1), we subjected the compounds into basic

• protecting groups in compounds 3a–l meet the criterion (1). For criterion (2), we conducted the Williamson ether formation reaction between compounds 4 and 1 to form compound 5 using KHMDS as the base in the presence of compounds 3a–l. Compound 4 (1 equiv) in THF was deprotonated with KHMDS (1.2 equiv). The

• compounds 3a–l against criteria (1) and (2), we concluded that the protecting groups in compounds 3a–g and 3i–l can be used as the base-labile protection group for the new PEG synthesis method featuring PEG elongation in one-pot. Among the groups studied, the phenethyl group (i.e., -(CH2)2Ph) is one of the

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• differences are discussed. Keywords: C–H functionalization; DABCO; HAT; photocatalysis; Introduction The functionalization of inert C–H bonds is a goal pursued by chemists from decades, due to its ubiquity in organic molecules. This strategy also dismisses tiresome protecting groups and functional group

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• a rich history that dates back decades [1][2][3][4][5]. Photochemical pathways allow access to diverse and interesting target structures [6][7][8][9][10], though photocleavage of C–X bonds for use as photoremovable protecting groups [11][12] has been the major thrust of the development of 2

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

• 73%. The structure of the trisaccharide was confirmed by comparison of its NMR and HRMS spectral data with that of the previously synthesized product by the linear strategy. With the protected trisaccharide 2 in hand, it remained to carry out the N-acetylation and the removal of the protecting groups

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• reaction to give the hydroxyfluorenone 10t (Scheme 6) was unsuccessful, suggesting that here TBHP chemoselectively reacts with the phenolic group to generate non-identifiable products. In order to provide an access to phenolic fluorenones as well, some commonly used phenol protecting groups were tested

• . Both TBS and SEM protecting groups were tolerated, as demonstrated by the syntheses of the fluorenones 10u and 10v (52 and 46% yields). As expected, the O-benzyl group was not tolerated, giving only trace amounts of product 10w, as benzyl ethers are well known to undergo side reactions with free

• Suzuki cross-coupling reactions, followed by reduction or reductive amination. The oxidative cyclization conditions are compatible with many functional groups on the aromatic rings (methoxy, chloro, cyano, nitro, and phenol protecting groups like TBS and SEM – but not benzyl and methylenedioxy

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• silyl ethers. Ooi et al. utilized an axially chiral organoaluminum Lewis acid catalyst (18) to convert a series of α,α-dialkyl-α-siloxyaldehydes 16 to α-siloxyketones 17 in high yields and >74% ee (Figure 5) [7]. This reaction is noteworthy for its tolerance of silyl protecting groups, which are

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• substrate with no residue R1 on the phenyl ring produced the corresponding product 4a in a higher yield than some the substituted substrates. In addition, N-protected (2-oxoindolin-3-yl) phosphate substrates could also deliver the products in good yield (see 4m–o), even though bulkier N-protecting groups

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

• for the introduction of unnatural modifications. However, the control over the length and substitution pattern remains poor. To ensure good regio- and stereoselectivity, the starting material, often a polycyclic compound, has to be designed with suitable protecting groups (PGs). These structures can

• importance of the deacetylated residues, with the free amino group able to stabilize new geometries. Many more N-protecting groups [217][261] are available and could generate COS with defined PA, however, to date most of them have shown significant drawbacks, decreasing the reactivity of the BB during

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

• appropriate chemoenzymatic syntheses [21][22][23]. Conclusion We have established synthetic access to a series of C6-tetrazole thioglycoside monosaccharide building blocks with capability for orthogonal C4- and tetrazole N-protecting groups. We demonstrate anomeric manipulation of these donors to new

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• group did not yield the desired product [22][23][24][25][26]. Several selective trityl deprotection attempts gave different results: either the reaction did not proceed at all yielding starting material, or both the trityl and benzyl group were removed or all three protecting groups were removed. Based

• pavettamine, in order to obtain the enantiomer. The final deprotection step proved particularly efficient, with two protecting groups being removed simultaneously to unveil the desired target. Structure of pavettamine 1 and its enantiomer 2. Crystal structure of compound 9. Single crystal X-ray structure of

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

• first hydrolyzed using NaOH followed by the reaction with TBDMSCl and benzoyl chloride to get the N6-benzoyl-3’,5’-O-diTBDMS-protected nucleoside 74. Removal of the silyl-protecting groups in the double-headed nucleoside 74 with TBAF in THF resulted in the formation of the desired doubled-headed

• was reduced in the presence of NaBH4 followed by the treatment with MsCl in pyridine to get the nucleoside salt 129. Next, the pyridinium group was replaced by an N3-protected thymine in basic medium followed by removal of the protecting groups and the selective DMTr protection of the C-5′-hydroxy

• simultaneous removal of tert-butyldimethylsilyl and amidine protecting groups, respectively (Scheme 41 and Scheme 42) [26]. The incorporation of the double-headed nucleosides 159 and 163 into oligonucleotides resulted in the formation of thermally stable DNA:RNA duplexes due to an efficient π–π stacking

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• , delivering the corresponding regioisomers 8l and 8l’ in 62% with 1:1.6 ratio. Moreover, the naphthalene and tetrahydroisoquinoline-derived acrylamides were also compatible, giving the polycyclic products 8m and 8n in 77% and 70%, respectively. Additionally, protecting groups such as isopropyl, benzyl, or

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

• We started our study by short screening of the glycosylation conditions in liquid SO2 (Table 1). To avoid a potential cleavage of acid-labile protecting groups and to obtain an easily analyzable reaction mixture, pivaloyl-protected mannosyl fluoride α-1a as a relatively stable disarmed glycosyl donor

• fluoride α-1a to form bis-mannosides α-8 in good yields (Scheme 2). In a series of pivaloyl-protected mannosides 3 a substrate-controlled α-selectivity due to the favoring effect of both neighboring ester-type protecting groups and the anomeric effect was observed [3]. On the other hand, mixing of glycosyl

• basic nitrogen or fluorophilic trimethylsilyl group in the molecule of the glycosyl acceptor (Figure S1, Supporting Information File 1). To our delight, no cleavage of the pivaloyl protecting groups in liquid SO2 medium was observed and the main side-product formed in the series of mannosides 3 was 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

• necessary protecting groups are present on the nucleobase and sugar moieties [76][77]. Unlike the phosphodiester linkage of natural DNA, the AM1 modification is an example of a non-ionic backbone. The crystal structure of a 13-mer RNA duplex with a single central AM1 modification revealed that this

• ]. Starting with a prepared 5'-iodo-4'-fluorouridine analogue that had been used in previous attempts of this synthesis, they removed the acetyl protecting groups at C3' and C2' with NH3/MeOH to give 5'-iodo-4'-fluorouridine [211]. Selective protection of the 2'-OH with TBDMS-Cl followed by protection of the

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

• removal of the side-chain protecting groups was achieved by using trifluoroacetic acid (TFA)/phenol/water/triisopropylsilane (TIPS) 88:5:5:2 (3 × 60 min). After cleavage, the remaining resin was extracted with DCM (2 × 10 min). All DCM extracts and TFA cleavages were combined, and the resulting mixture

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

• immunologically unfavorable cytosine (C), is needed. The preparation of all four phosphoramidites (A, G, mC, and T) is generally not easy because each nucleobase differs in the sensitivity to reactions, and appropriate protecting groups need to be selected [8][21][22][23]. We recently achieved the synthesis of

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• 9α-hydroxylated diol. The following oxidative cleavage of the C–C bond with a mild oxidant leads to the steroid with an appropriately broken steroid skeleton. The method provides the target compound in only two steps, without any manipulations involving protecting groups. The present method features

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• (5.0 equiv). The excess of base and alcohol was required due to the cleavage of acetyl protecting groups. Products 3g–i were obtained in yields of up to 79% (Scheme 4). Furthermore, purification of the products 3g–i was complicated due to their poor solubility in organic solvents. The C6

• regioselectivity of SNAr reactions was proved by 13C NMR comparison of the products 3a–i with similar compounds from literature [61]. Intriguingly, we were able to conserve the acetate protecting groups in product 3j, when the SNAr reaction was performed in the presence of DBU used as base. The artificial

• dinucleotide analogue 3j was obtained in 25% isolated yield. We have explored also reactions of 2,6-bistriazolylpurines 2a and 2c with water in buffered and basic medium, respectively (Scheme 5). The buffered conditions (NaOAc/DMSO/H2O) were sufficiently mild to maintain the acetyl protecting groups in product

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• aliphatic amino acid, (E)-2-amino-5-(pentafluorosulfanyl)pent-4-enoic acid (14, Figure 1), SF5NVa [21]. Most recently, Cobb et al. [22] reported the synthesis of several pentafluorosulfanyl phenylalanine derivatives with suitable protecting groups to allow incorporation into peptides through common solid

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

• analysis, we envisioned a Suzuki coupling of two suitably substituted arenes. Silyl protecting groups like the tert-butyldimethylsilyl group (TBS) were considered appropriate for all projected reaction steps. The boronate moiety 6a was prepared starting with 4-methylcatechol (2), which was initially