Phosphoramidite building blocks with protected nitroxides for the synthesis of spin-labeled DNA and RNA

• Timo Weinrich,
• Eva A. Jaumann,
• Ute M. Scheffer,
• Thomas F. Prisner and
• Michael W. Göbel

Beilstein J. Org. Chem. 2018, 14, 1563–1569, doi:10.3762/bjoc.14.133

• therefore developed a third strategy based on photolabile protective groups [41][42][43] finally leading to phosphoramidite 6. This building block behaves in solid-phase RNA synthesis as any normal TOM protected amidite. It is completely stable against the conditions used for strand assembly, RNA

• . Results and Discussion To prepare compound 5, the deoxyuridine derivative 9 [44] was activated by sulfonylation and then treated with the protected TEMPO building block 10 [43] to provide 11 (Scheme 1). After deacetylation, phosphitylation of 12 straightforwardly led to amidite 5 in multigram amounts. In

• 6-chloro derivative 13 as starting material, easily accessible from deoxyadenosine via enzymatic deamination, acetylation [37] and chlorination. This compound reacted cleanly and yielded 67% of the TEMPO conjugate 14. After deacetylation (15) and tritylation (16), amidite building block 7 was

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• of the first studies documenting the use of the iodoarene moiety as a building block in synthesis has been reported in 2004. The λ5-iodane reagent IBX has been shown to promote the α-functionalization of ketones following the introduction of the 2-iodobenzoic acid motif (Scheme 2a) [28]. Mono- and

• indoles with diaryl-λ3-iodanes (Scheme 36) [75]. The reaction first involves the use of 20 mol % of CuI and 1.1 equivalents of di-tert-butylpyridine (dtbpy) to convert the indole to the C3–H arylated product. The released Ar–I building block, then, can be engaged in the subsequent step of N–H arylation by

Cobalt–metalloid alloys for electrochemical oxidation of 5-hydroxymethylfurfural as an alternative anode reaction in lieu of oxygen evolution during water splitting

• Jonas Weidner,
• Stefan Barwe,
• Kirill Sliozberg,
• Stefan Piontek,
• Justus Masa,
• Ulf-Peter Apfel and
• Wolfgang Schuhmann

Beilstein J. Org. Chem. 2018, 14, 1436–1445, doi:10.3762/bjoc.14.121

• -refinery based chemicals for a “green” chemical industry [6][7][8]. FDCA was suggested to replace, e.g., terephthalic acid as building block for the formation of polyamides, polyesters, and polyurethanes [6]. Especially, the polymer polyethylene terephthalate (PET), a perpetually used polymer, could be

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• siderophore antibiotic D-fluviabactin, the cytotoxic agent westiellamide, the antifungal macrodiolide leupyrrin A1 and the antitumour compound BE-70016 (Figure 1). In addition, synthetic polymers based on the 2-oxazoline building block constitute versatile platforms for a range of biomedical applications

Polysubstituted ferrocenes as tunable redox mediators

• Sven D. Waniek,
• Jan Klett,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2018, 14, 1004–1015, doi:10.3762/bjoc.14.86

• electrosynthesis. Keywords: cyclic voltammetry; ferrocene; paramagnetic NMR spectroscopy; redox mediator; spectroelectrochemistry; Introduction Since its discovery, ferrocene (FcH) has been established as versatile redox-active building block [1][2][3]. Ferrocene can be reversibly oxidized to the 17 valence

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• them. We aim to offer basic and integral knowledge on the rational design towards the construction of PDCs through analyzing each building block, as also to highlight the overall progress of this rapidly growing field. Therefore, we focus on several intriguing examples from the recent literature

• on its building block 2-pyrrolino-DOX and tried to construct new PDCs using other peptides. Therefore, they synthesized a new analog, designated AN-238, consisting of the octapeptide RC-121 linked through the α-amino group of its N-terminal D-Phe moiety and a glutaric acid spacer to the 14-OH group

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• )- or (S)-2,3-isopropylideneglyceraldehyde with a second chiral building block containing the amine function, followed by dihydroxylation [13][14]. Despite the compounds already available through these and other approaches, novel synthetic concepts to fill the remaining methodological gaps for accessing

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• acids. Shown is the monomeric building block of nucleic acids. Changes to the nucleotide structure can affect molecular recognition, as well as structure and function. Formation of oxocarbenium ion during glycosidic bond cleavage in nucleosides [31]. The extent of leaving group stabilization and

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• crystallization (70% yield, >96% de). Lactam (2R,3S)-25 bearing a α-methyl-para-methoxyphenyl chiral auxiliary was then deprotected with trifluoroacetic acid at room temperature to deliver the NH-free isoindolinone (3S)-26 (76% yield, 98% ee) which is a key building block in the synthesis of benzodiazepine

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• effectively when the sugar at the reducing terminus has a galacto configuration [48][49][50]. Production of unprotected N-glycan oxazolines by total synthesis The majority of the reported syntheses of N-glycan oxazolines have employed a key selectively protected Manβ(1–4)GlcNAc disaccharide building block

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• allows the preparation of the trinucleotide, its conversion into a coupling competent building block, and its subsequent use in chemical DNA synthesis. Trinucleotides have been prepared in solution [19], on solid phase [20], and more recently on soluble polymers [21][22][23] (Figure 1), followed by

• solvents and to precipitate upon the addition of a polar solvent, typically methanol. After coupling of a standard phosphoramidite building block followed by oxidation with 2-butanone peroxide in dichloromethane, the resulting dimer on the support was again precipitated with methanol and filtered, before

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• compatible with the metalation reagent, the corresponding benzyl ether 3 was selected as central building block. Results and Discussion In our previous work we prepared isoquinoline 3 in a three-step procedure starting from commercially available O-benzylisovanillin (2) in a modified Pomeranz–Fritsch

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• protection and phosphitylation using CEP-Cl generated the fully protected monomer ready for solid-phase synthesis [50]. The complete synthesis of the RNA building block of tCO was in this way achieved over five steps with a total yield of 28%, improved from the four step DNA building block synthesis of tCO

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• opening; fluorinated building block; vicinal difluoride; Introduction The introduction of fluorine in organic compounds usually results in the modification of a range of chemical, physical and biological properties [1]. Fluorine incorporation is therefore a common strategy to optimise the properties of

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• useful [11][12][13][14]. A building-block approach remains an alternative strategy to the synthesis of fluorine-containing compounds. This complementary method takes advantage of specific reagents featuring original fluorinated motives and/or functional groups which affords more complex derivatives via

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• fluoroalkylated allylic compounds can serve as a versatile building block for the synthesis of complex fluorinated molecules [36][37]. Herein, we describe a palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides. The reaction proceeds under mild reaction conditions with broad

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• , France Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France 10.3762/bjoc.13.217 Abstract Ball milling was exploited to prepare a substituted proline building block by mechanochemical nucleophilic substitution

• preparation of substituted Pro–Pro DKPs. For this purpose, we considered using dimethyl (2R,5S)-pyrrolidine-2,5-dicarboxylate (cis-11) as a building block in the synthesis of dipeptides and diketopiperazines. This building block was used in a very limited number of cases for the formation of DKP in

• ratio (cis-11/trans-11) was different when the reaction was performed in solution (Table 2, entry 1) or in the ball mill (Table 2, entries 2–9) with a higher selectivity in the latter case [42]. With this building block in hands, the preparation of a variety of DKPs could be envisaged (Scheme 4

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• the alternate preparation of (S)-2-aminohept-6-enoate ester as a building block and its diversification through a cross-metathesis reaction to prepare the title compounds. The utility of the protocol is demonstrated through the preparation of three suberic acid derivatives of relevance to the design

• therefore the variation in the carbonyl functionality may have implications in drug design. Moreover, Asu and its congener 2-aminopimelic acid have been used as ethylenic equivalent of a disulfide linkage [4]. Other applications of Asu in peptide engineering and as a building block are of notable importance

• applications remains important. During the course of our work on the synthesis of amino acids and peptides relevant to HDAC inhibition [12], we required orthogonally protected Asu derivatives. Herein we describe an alternate synthesis of the important building block 2-aminoheptenoic acid and its application to

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• disaccharide 7, which could be subjected to bromine-promoted glycosylation for further chain elongation. As an example, preactivation of a monosaccharide 8 with bromine was followed by the addition of a bifunctional disaccharide building block 10 and subsequent TMSOTf-promoted orthoester rearrangement

• transformations commonly encountered in building block preparation [41]. At the same time, mild promoters are available for thioglycoside activation. The anomeric reactivities of thioglycosides towards glycosylation can be significantly influenced by the protective groups on the glycan ring as well as the size

• prepare building blocks with the required anomeric reactivities. Furthermore, the relative anomeric reactivity values of a building block can vary depending on the structures of acceptors and reaction condition [44], presenting challenges in accurately predicting the reaction outcome. The aforementioned

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• activation of the S-ethyl leaving group in compound 55 was achieved with MeOTf and the glycosylation of the central building block took place with concomitant removal of the p-methoxybenzyl (PMB) group. The o-allylphenyl leaving group was activated with NIS/TfOH, and again the PMB group of the acceptor was

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• building block 8 followed by UV-cleavage, disaccharide 16 was obtained in 63% isolated yield. Moreover, DBDMH performs as well as N-iodosuccinimide (NIS) in activating phenyl selenoglycoside 17 in the presence of water to furnish hemiacetal 18 en route to glycosyl imidate 19 (Scheme 2). Conclusion The

• compounds. Acknowledgements We gratefully acknowledge the Max Planck Society for financial support. We thank Dr. Martina Delbianco for help with automated glycan assembly, Ms. Priya Bharate for providing building block 8, Dr. Madhu Emmadi for building block 17, Dr. Lennart Lykke for building block 9 and Ms

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• amines were safely controlled at maximum contacts (solvent-free) by the acid salt NaHSO4. Using 2.0 equiv of both NaHSO4 and PIDA, 72–92% of amides were isolated within 2 h (Scheme 17) [81]. Amino acids are one of the important biomolecules for example as building block of peptides and proteins [75][82

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• ), 34.1 (C-7), 32.7 (C-8), 22.4 (Me-6), 21.4 (Me-16), 13.8 (Me-10); HRMS (ESI+): calcd. for [C17H24NO2S]+: 306.1528; found: 306.1529. Isoprene as chemical building block in nature and organic synthesis. Pd-catalyzed dimerization of isoprene. Putative mechanism for the Pd(OAc)2-catalyzed dimerization of

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• alkaloids one common building block, (4-methoxy-2-(methoxycarbonyl)phenyl)boronic acid pinacol ester (9) [24], could be applied, since the alkaloids of interest all bear the methoxy group at C-9. Suzuki cross-coupling reaction of the iodinated isoquinolines 8a–c with this boronate under Pd(PPh3)4 catalysis