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

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• development of the all-carbon [3 + 2] cyclization with the reactive functional groups’ compatibilities and/or without the use of protecting groups [83][84] can improve the synthetic efficiency and make this class of reactions more attractive to the synthetic scientist for applications. Lastly, we anticipate

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

• being preferentially formed. Optimization of the protection scheme lead to a new and economic route to the desired C8-alkynylated building block and its incorporation in RNA. Keywords: nucleoside chemistry; protecting groups; RNA synthesis; Sonogashira reaction; Introduction Oligoribonucleotides

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• synthesis (SPPS) [47] to produce the peptides shown in Scheme 1. We first synthesized the peptide segments (i.e., Fmoc-DEDDDLLIG (1a) and acetyl-DEDDDLLIG (2a)). We kept the tert-butyl protecting groups of aspartic acid for the coupling reaction with Nap-ffky. We used 2,2,2-trifluoroethanol (TFE) in

• , we used TFA at room temperature for 2 h to cleave the tert-butyl protecting groups of 1b and 2b. After adding diethyl ether to precipitate the crude peptides, centrifugation, and washing three times, we used reversed-phase HPLC and acetonitrile (containing 0.1% TFA) and double-distilled water

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

• tendency to migrate and a generally higher stability with respect to thiol-containing AuNPs [37][38][39]. A further advantage is the straightforward ligand synthesis, which does not require the use of protecting groups as in the case of thiols. The ligand 1 served as the solubilizing component and was

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• -iodophenylazo)-4-chloropyridine (17) with LiSSiMe3 (8) [28], t-BuSH (13) and HSCH2CH2CO2CH3 (15) [29]. Electron-deficient aromatic, silylated thiols exhibit very labile Si–S bonds [30]. Thus, even bulky silyl protection groups are not suitable as protecting groups for the subsequent Suzuki reaction

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• related esters are relevant synthetic building blocks widely employed as cross-coupling reagents [14] as well as protecting groups for polyols and diamines [15][16]. Moreover, the reversible covalent interaction of boronic acids with specifically oriented cis-1,2 and 1,3-diols has been successfully

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

• with Selectfluor® [153]. The authors justified the use of protecting groups due to their extensive use in peptide synthesis. Of all the PGs tested, phthalimide (Phth)- and trifluoroacetate (TFA)-protected substrates underwent photosensitized C–H fluorination to give the highest yield of 80% and 71% of

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• manipulation of the C-4 and C-6 protecting groups gave the secondary allylic alcohol 71, which underwent an epoxidation with mCPBA to give 72. A second sequence of C-4/C-6 protection, manipulation, and oxidation gave the aldehyde 73. The disadvantages of this route include the overall length (13 or 14 steps

• ) gave the C-phenyl glucoside 75 [36]. Notably, the use of oxidants other than BQ gave either the TMS enol ether or the 2,3-dihydro-6-phenyl-4H-pyran-4-one. The C-3 exocyclic methylene group was introduced by a Wittig olefination, and after the manipulation of the protecting groups, a VO(acac)2-catalyzed

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

• -chloroperbenzoic acid (m-CPBA, 12 equiv) led to the simultaneous phosphorylation of the hydroxy group and to the oxidation of the sulfide to give 1-O-dibenzyloxyphosphoryl-ᴅ-fructofuranosyl sulfones 7α, 8α, 8β and 9α in excellent yields (Scheme 1). Final removal of benzyl protecting groups by catalytic

• of the benzyl protecting groups in later stages of the synthesis. This advantage makes the overall synthesis of the target molecules one reaction step shorter in comparison with the synthesis starting from pivalate 11 (Scheme 3). With alcohols 17 in hand, the synthesis continued with their

• obtained by acetonide hydrolysis under acidic conditions followed by the final catalytic hydrogenation of the benzyl protecting groups in derivatives 22. Evaluation of the effects of the target compounds on the synthesis of lipid-linked galactan precursors The availability of a series of compounds with

Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies

• Giovanni Picca,
• Markus Probst,
• Simon M. Langenegger,
• Oleg Khorev,
• Peter Bütikofer,
• Anant K. Menon and
• Robert Häner

Beilstein J. Org. Chem. 2020, 16, 1732–1739, doi:10.3762/bjoc.16.145

• MPC-2. There, the NBD tag was only partially stable to the conditions used to remove the protecting groups in the final step (NH3 in MeOH, Figure 3). Under such alkaline conditions, a considerable amount of degradation of NBD was observed, making an additional purification step necessary to obtain

• (DCM), and ETT served as the activator. The subsequent oxidation of the unstable phosphite triester to the more stable phosphotriester was performed with t-BuOOH. The resulting intermediates were then treated overnight with a solution of ammonia in methanol to remove the protecting groups. An overall

• t-BuOOH, and finally, the protecting groups were removed under basic conditions to give either MPC-1 or MPC-2 as ammonium salts. ETT = 5-(ethylthio)-1H-tetrazole. Preparation of mannosyl phosphoramidites. Starting from 2,3,4,6-tetra-O-acetyl-β-ᴅ-mannopyranose (β-4Ac-Man), the phosphitylation using 2

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

• CXC peptide building block design (single-letter code) were the terminal amino acids are cysteine (C) and the X can be any amino acid (Scheme 1a). This allows for rapid synthesis of various new building bocks by standard Fmoc based SPPS using Trt protecting groups for cysteine, which are subsequently

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

• 43 to generate 44. The isotope exchange was explored by using [18F]-TBA in DMF at 130 °C for 10 min to give [18F]-44. Decarbonylation of 44 was achieved by treatment with Rh(PPh3)3Cl to afford 45 and the subsequent removal of protecting groups gave 46. Conventional reactions yielded the desired

• 148 in variable yields with partial racemization. Phthalimido and trifluoroacetyl N-terminal protecting groups (R1 = Phth or TFA) and unprotected C-terminal derivatives (R2 = H) provided the most efficient outcomes (80 and 67% yield, respectively). An N-acetyl group was also suitable as protecting

• 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

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• efficient one to achieve an enantioselectivity of up to 96% ee. Interestingly, piperidones with different carbamate protecting groups (Me, Et, Ph, tosyl, and Bn, respectively) were tolerated, and a high enantioselectivity could also be obtained with several other dialkylzinc reagents (e.g., iPr2Zn and n

• reagents and protecting groups were examined, providing the products with good yield (up to 90%) and ee (up to 95%). Copper-catalysed conjugate addition reactions to alkenyl-substituted heterocycles Chiral heterocyclic aromatic compounds are crucial motifs in natural products and bioactive molecules, and

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• containing glycopeptides were prepared in solution. The applicability of two common peptide coupling reagents, using an orthogonal Fmoc/t-Bu strategy along with acetyl protecting groups for the carbohydrate moiety, was studied. Thus, the prepared libraries of glycopeptides were designed as model systems of

• . The treatment of the glycosylated tripeptides 6a–f and 7a–f with a mixture of TFA, DCM, and H2O (10:10:1) [31] afforded the partially deprotected acids 8a–f and 9a–f in quantitative yields. The final deprotection of both the base-labile acetyl and Fmoc-protecting groups was achieved by the treatment

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• group were investigated. Instead of the N-phenyl group, other protecting groups such as acetyl, benzoyl, or carbamates were tested, but the corresponding starting materials proved to be unreactive in the desired transformation. The use of substituted N-phenyl groups revealed that almost all of the

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• bromide or n-pentyltriphenylphosphonium bromide followed by reduction of the double bonds were performed first giving derivatives 24 and 25 containing the shorter carbon chains of the pheromones. Aldehydes 26 and 27 were obtained after removal of the protecting groups from the alcohols in compounds 24 and

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• protecting groups [12]. Later, ruthenium complexes-catalyzed alkyne–azide cycloadditions (RuAACs) regioselectively produced the opposite form of the disubstituted triazoles. Thus, a wide range of azides was reacted with diverse nonactivated terminal alkyne substrates using ruthenium complexes to generate

Convenient synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia albertii O4

• Tapasi Manna,
• Arin Gucchait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 106–110, doi:10.3762/bjoc.16.12

• protic acid glycosyl activator. The expected configuration at the glycosidic linkages was achieved using a reasonable selection of protecting groups in the manosaccharide intermediates. Keywords: Escherichia albertii O4; glycosylation; HClO4/SiO2; O-antigen; pentasaccharide; Introduction Diarrheal

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• phosphonate ester derivatives 13 and 15 in good yields. For the future synthesis of deprotected glycal ester derivatives containing prenyl units, benzyl groups will have to be exchanged for protecting groups that can be removed under nonhydrogenolytic conditions, e.g., silyl ether protecting groups. In

• preliminary experiments, Lewis acid cleavage using BBr3, BCl3, and TiCl4, respectively, was not successful, although the latter reagent had previously been used to deprotect two benzyl groups from an allyl glycoside containing a 4-amino-4-deoxy-ʟ-arabinose residue [36]. Cleavage of the benzyl protecting

• groups with concomitant reduction of the azido group afforded the α-anomeric octyl ((4-amino-4-deoxy-ʟ-arabinopyranosyl)methyl)phosphonate 16 in 38% yield. Deprotection of the endo-glycal ester 15 was also investigated. An intermediate enol resulting from hydrogenolytic cleavage of the benzyl ether was

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• order to access glycans in a pure form. In line with this, various C-5-substituted 2,7-anhydrosialic acid derivatives bearing both electron-donating and -withdrawing protecting groups were synthesized and subjected to different Lewis acid-catalyzed solvent-free ring-opening reactions at room temperature

• crystallography, compounds 2 and 3 were acetylated with Ac2O in the presence of a catalytic amount of 4-(dimethylamino)pyridine (DMAP) in pyridine to give 5 [6] and 6 in 75 and 77% yield, respectively (Scheme 1), and the compatibility of acetyl protecting groups with the Lewis acids during acetolysis reactions

• -benzoylation of 2 with benzoyl chloride in pyridine produced compound 9 in a moderate yield of 57% (Scheme 2) [34]. Wong and co-workers reported the major effects of the carboxy group on the anomeric reactivity of sialic acid compared with the side chain protecting groups. Hence, we converted 2 into O-acetyl