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

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• devoted to the synthesis of new MraY inhibitors [49][50], we were interested in developing a more efficient access to 5’-ethynyluridine, a crucial building block for the further synthesis of triazole-containing compounds [49]. Intrigued by the moderate diastereomeric ratio reported for the addition or

• reagent, we manage to obtain an excellent diastereoselectivity. Indeed, by using the most bulky 2’,3’-O-TIPS protecting groups and TIPS-ethynylmagnesium bromide, the 5’-ethynylation was achieved in a 99:1 ratio in favor of the 5’S-isomer. The resulting building block with a broad potential in nucleos(t

Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• conditions [7], in this case the results were not significantly better, as shown in Table 3. Having set up the conditions for the synthesis of isochromanones, we moved to explore the possibility to obtain isobenzofuranones 13 by introducing an ester functional group in the alkene building block, according to

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• should be generated by nucleophilic addition of an allyl anion equivalent to the resulting aldehyde 5. Guanidine formation and ozonolysis with subsequent oxidation to the carboxylic acid would then furnish the protected GHPD side chain building block 3 which can then be coupled to the cyclodepsipeptide

• chain [12]. In order to reduce the number of linear steps, the protected guanidino group was included in the side chain building block in our case. This strategy would allow to assemble the complete peptide core in a solid-phase synthesis and to perform the solution-phase coupling without a large excess

• of the GHPD side chain building block. Thus, Cudic’s SPPS approach should be combined with the advantages of the late stage coupling employed by Jolliffe. Synthesis The C13-fragment was prepared starting from erucamide (6) in three simple operations. Reduction of the amide with lithium aluminium

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• has been regarded as an approach that could combine the advantageous features of both the solution and solid-phase syntheses. The critical step of this approach is the separation of the support-anchored oligonucleotide chain from the monomeric building block and other small molecular reagents and

• order by esterification of phosphoric acid with the 3´-OH of one and the 5´-OH of the other nucleoside. Usually, the 3´-OH is first esterified with an appropriate derivative of phosphoric acid and the resulting building block is then reacted with the 5´-OH (Figure 1). Either a linear or a convergent

• the nucleobases are usually protected with acyl groups and the 5´-OH of the monomeric building block with a 4,4’-dimethoxytrityl group (DMTr), or sometimes with its monomethoxytrityl analog (MMTr) [4][5]. To achieve coupling, phosphoramidites are activated with azoles [6], such as tetrazole [7], its

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• , containing Tb, ChL and BODIPY, represents a well-defined traceable system with a potentiated ability to assemble into liposomal systems. Results and Discussion Chemistry In this work, Tb was connected to a pegylated BODIPY building block containing ChL. This way obtained construct 6 was used as a component

• for liposomal formulation. The syntheses of some of the employed molecules were previously described [24][27][28], their structures are shown in Figure 1. The synthesis of a BODIPY-based building block is displayed in Scheme 1, part A. Methyl 4-iodo-L-phenylalaninate hydrochloride was prepared by the

• hydrolysis of methyl ester 1 with aqueous LiOH in THF and subsequent Suzuki cross-coupling with BODIPY-BA [34] catalyzed by Pd(PPh3)4 and K2CO3 in a mixture of toluene/MeOH/water provided the fluorescent building block 3 in 88% yield. Sequential connection of other functional components of the target

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• . Results and Discussion The improved synthesis utilizes the Suzuki–Miyaura cross-coupling reaction to merge the western fragment derived from ketone 9 with the newly designed eastern building block 13. This fragment was obtained in very good yield from vinyl iodide 12 [9] by a Stille protocol using doubly

• elansolid B1 (2). The improvements are mainly associated with the preparation of the triene unit at C10–C15 by utilizing the Stille and the Suzuki–Miyaura cross-coupling reactions as well as the highly versatile difunctionalized building block 14. In principal, the synthesis sheds light on how such (Z,E,Z

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• , there is no available methodology to obtain this building block using chemical hydrolysis. We produced compound 9 by hydrolysis of the previously synthesized glycamine 7. In addition, we conducted a stepwise sequence of hydrolysis and reduction reactions, followed by periodate cleavage of the 1,2

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• , chosen such that the IGS of one pair is matched to the target sites of the next pair. In this way one ribozyme, say E1, can catalyze the formation of the next ribozyme, E2, from its non-covalently bound building blocks I2. This ribozyme can in turn catalyze the formation of E3 from its building block and

• building blocks consist of an aromatic core that is functionalized with two thiol groups and a peptide chain (Figure 12a). Building block 1 and 2 are very closely related to each other and differ only in a single amino acid of the peptide chain. These peptide building blocks can then be oxidized to form

• doubled, leading to an exponential self-replication. In previous work it was already shown that the less hydrophobic building block 2 tends to form larger octameric macrocycles than the more hydrophobic building block 1 which forms hexamers [54]. This is reasonable, since a weaker hydrophobic interaction