Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• available purity and used as such. A detailed synthetic strategy for Fmoc-TfIle-OH is described in literature [44]. For the synthesis of Fmoc-HfLeu-OH see Supporting Information File 1. Peptide synthesis, purification and characterization Peptides were synthesized manually in a 0.05 mmol scale on a solid

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• nucleophiles such as nucleoside mono-, -di- or -triphosphates and are typically reacted in anhydrous DMF in the presence of zinc chloride. The GMP imidazolide (18) is reacted with m7GDP (17) in the presence of ZnCl2 as catalyst to yield m7GpppG (12) [49]. In the past years, variations of this general synthetic

• strategy were used to obtain numerous cap analogues. Among the most interesting modifications is the above-mentioned anti-reverse cap analogue (ARCA) and GpppG which are commercially available. In addition, cap analogues with improved properties – namely binding to eIF4E, translational efficiency, and

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

• decarboxylative addition of malonic acid mono(thio)esters to aldehydes and imines has become an increasingly popular synthetic strategy [28][30][31][32][33][34][35][36]. However, the utility of trifluoromethylketimines as electrophilic substrates in this reaction remains underinvestigated. The only published work

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• the desired product 8 through the action of a reactive carbonyl donor such as CDI (1,1′-carbonyldiimidazole) or triphosgene (bis(trichloromethyl)carbonate). This synthetic strategy presented various advantages as it relies on readily available substrates and reagents, creates small amounts of non

• cyclisation products 12 and 14, assigned structure of byproduct 15. Synthetic strategy towards desired indole product 8. Initial flow reactor setup for the synthesis of intermediate 11. Coflore ACR setup for the synthesis of intermediate 11. Quenching and work-up of the reaction stream from the Coflore ACR

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• mechanochemical synthetic strategy and applied it to a previously unknown carbodiimide insertion into sulfonimides, resulting in two-atom ring expansion and chain extension reactions [51]. Saccharin was selected as a model cyclic sulfonimide substrate, while 4-methyl-N-tosylbenzamide was employed as an acyclic

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• perspective, however, urges an approach using a synthetic strategy based on the stepwise build-up of complex molecular systems. We envision the development of a toolbox that allows us to go beyond describing and understanding systems, extending to the rational design of function arising from a collection of

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• enantiomerically pure synthesis of the heterocyclic core of the D-series GE2270 is reported. The synthetic strategy combines the Hantzsch thiazole’s building condensation with a cross-coupling reaction including direct C–H hetarylation to build and connect step-by-step thiazolyl moieties to the 5-bromopicolinate

• ’-bithiazole appendage [20]. In 2009, we have reported an original access to micrococcinate ester (R = Et) from ready available ethyl 5-bromo picolinate (Figure 1) [21][22]. The synthetic strategy was based upon the step-by-step direct introduction and building of thiazolyl units onto a pyridine central core

• improved synthetic strategy toward the structurally-related micrococcinate ester bearing a methyl ketone function (R = Me) was reported through building and direct introduction of thiazole units using BSC and Hantzsch methodologies. The final access to a novel fully orthogonally-protected heterocyclic core

Sugar-based micro/mesoporous hypercross-linked polymers with in situ embedded silver nanoparticles for catalytic reduction

• Qing Yin,
• Qi Chen,
• Li-Can Lu and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 1212–1221, doi:10.3762/bjoc.13.120

• -linkers [4], and self-polycondensation of small molecular monomers [5]. Since the Tan group proposed the new synthetic strategy that "knits" low functionality rigid aromatic compounds with formaldehyde dimethyl acetal (FDA) as an external cross-linking agent through a Friedel–Crafts reaction to synthesize

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• dichloromethane. Comparison of the relative energies given in Figure 8, shows that the formation of 19c is plausible under the given reaction conditions in dichloromethane. Conclusion The synthetic strategy described in this paper shows the importance of intramolecular alkyne cyclization for the formation of

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• synthesis of biologically interesting heterocycles [43][44][45][46][47], we were interested in a practical synthetic strategy towards imidazo[1,2-a]pyridine-fused isoquinoline systems. We believe that this type of polycyclic systems may have interesting biological profiles [48]. Herein, we report our recent

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• addition to overcoming the setback associated with inefficient sulfonylation, we showed that other changes in the subsequent steps of the synthetic strategy can further improve the overall N-methylation process. This development enabled the methylation of various amine motifs on solid support and allowed

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• Herein, we report the development of a synthetic strategy using [4 + 2]-cycloaddition reactions to yield endoperoxides 18–23 that contain a protected primary amine. Such intermediates serve as useful new building blocks for organic synthesis. Preliminary exploration of the chemistry of these compounds

• marketed drugs Glyset and Zavesca. Bottom: Our synthetic strategy aimed to explore substituted endoperoxides (e.g. dihydroxylated endoperoxide, box) as key intermediates for the divergent synthesis of novel azasugars. PG = protection group. Synthesis of Boc- and Pht-protected diene substrates for

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• consensus synthetic strategy for 1a involves the convergent assembly of chroman-based key subunits, the question of how best to access them remains open. The intramolecular ring-opening of enantiomerically pure epoxides by the phenolic hydroxy group is one of the most popular methods to construct 3 (Scheme

A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

• Arno Verlee,
• Thomas Heugebaert,
• Tom van der Meer,
• Pavel I. Kerchev,
• Frank Van Breusegem and
• Christian V. Stevens

Beilstein J. Org. Chem. 2017, 13, 303–312, doi:10.3762/bjoc.13.33

• )benzoic acid [15][16][17]. This synthetic approach is a two-step procedure and therefore needs two subsequent work-up steps, limiting the yield and resulting in a more time-consuming synthetic approach. Yang et al. [18] reported a one-pot synthetic strategy for m-sulfamoylbenzamide analogues starting from

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• azido group following β-glucoside formation [23]. Alternatively, a linear synthetic strategy in which the sterically hindered C4 hydroxy group would be glycosylated first, followed by the C3 hydroxy group of β-mannosazide building block 4, was designed in case the convergent approach proved unsuccessful

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot

• Philip J. Kitson,
• Stefan Glatzel and
• Leroy Cronin

Beilstein J. Org. Chem. 2016, 12, 2776–2783, doi:10.3762/bjoc.12.276

• software developed for the robot. It was determined that the minimum number of pumps necessary to effect the synthesis of ibuprofen by our chosen route was five, to accommodate the starting materials and reagents required. Synthetic strategy The synthesis modified for use with our automated synthetic

Green chemistry

• Luigi Vaccaro

Beilstein J. Org. Chem. 2016, 12, 2763–2765, doi:10.3762/bjoc.12.273

• of the waste generated, which is derived from both the synthetic strategy and the technology used. The fundamental role of green metrics is to evaluate the modern classification of chemical transformations in relation to the potential or actual pollution produced. In some cases, such as calculating

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• is of interest for their identification to compare mass spectra of positional isomers of unsaturated macrolactones. Furthermore, a fast synthetic strategy is needed to synthesize various isomers. In the present work we describe 1) the identification of macrolides from H. cinnamomeoventris, 2) discuss

• opted to synthesize 2 as well. To allow later enantiomer determination of A, an enantioselective synthetic strategy was followed. Several synthetic routes for the synthesis of 1 have been reported [16][17][18][19][20]. These syntheses were performed before the advent of ring-closing metathesis (RCM

• )-configured double bond, although in moderate yield (see Supporting Information File 1 for full experimental data). A similar synthetic strategy was applied for the synthesis of macrolide 1 (Scheme 2). The stereogenic center was introduced using commercially available (R)-propylene oxide (13) as starting

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• synthetic strategy started from silylated serinol 70 to which the mannosyl unit was attached to afford glycosylamine 71, prior to construction of the cyclic guanidine motif and amino acid functionality. With glycosylamine 71 in hand, attention turned to installation of the guanidine moiety. Treatment of 71

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• functional groups into its native structure [10][11]. Such chemically modified oligonucleotides are useful intermediates for their subsequent functionalization through post-synthetic protocols [11][12][13]. Within a post-synthetic strategy, a nucleotide analog is modified with a reactive functional group

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• diastereomer using a highly efficient and stereocontrolled synthetic strategy to construct the desired bis-THF ring building block 73 in two steps (Scheme 15) [120][121]. Thus, starting from commercially available trans-1,5,9-decatriene (71) a stereo- and positionselective Sharpless AD reaction [86][87][88

• assembled in a further 10 steps (Scheme 15) [120][121]. Subsequently, Shi and co-workers successfully applied their synthetic strategy to the first total synthesis of gigantetrocin A (76) [122][123], a mono-THF acetogenin, isolated from Goniothalamus giganteus by McLaughlin and co-workers [124]. This time

Bridgehead vicinal diallylation of norbornene derivatives and extension to propellane derivatives via ring-closing metathesis

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2016, 12, 1877–1883, doi:10.3762/bjoc.12.177

• Sambasivarao Kotha Rama Gunta Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai, India 10.3762/bjoc.12.177 Abstract Here, we report a simple synthetic strategy to the bridgehead vicinal diallylation of norbornene derivatives. These substrates are useful to generate

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• unusual 2,3-pyrrolidinedione system and developed a synthetic strategy towards new lead compounds with antimicrobial activity. Efforts to synthesize analogues to build a structure–activity relationship (SAR) profile and optimize the activity are underway. Structure of leopolic acid A. Synthesis of

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• presence of Lewis acids is a common synthetic strategy for making pyrans and furans. Hemiacetals are also biosynthesis intermediates where they are transformed into individually functionalised heterocycles or acetals. In many cases, these hemiacetals are also appropriately activated to react further

Stereodynamic tetrahydrobiisoindole “NU-BIPHEP(O)”s: functionalization, rotational barriers and non-covalent interactions

• Golo Storch,
• Sebastian Pallmann,
• Frank Rominger and
• Oliver Trapp

Beilstein J. Org. Chem. 2016, 12, 1453–1458, doi:10.3762/bjoc.12.141

• paper, we describe the application of Doherty’s synthetic strategy for the synthesis of stereodynamic tetrahydrobiisoindole “NU-BIPHEP(O)” compounds bearing secondary amino groups for functionalization. The attachment of a 3,5-dichlorobenzoyl binding site is reported and non-covalent interactions as