A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• prodrug 2, bearing ~3 δ-aminolevulinic acid moieties per β-CD macrocycle. The dual nature of the system was exemplified by the intracellular formation of PpIX using “intracellular chemical synthesis”. At the same time 2 was able to carry inside the cytoplasm a model guest molecule. The possibility that

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• units might be required to fully mimic the polysaccharide activity, and paves the ground for a deeper understanding of the structural requirements needed to develop a conjugate vaccine based on well-defined oligosaccharides attained by chemical synthesis. The preparation of these longer chain MenX

• of the hemiacetal under these reaction conditions. Compound 9 was subjected to Zemplén transesterification with NaOMe in methanol to afford alcohol 10, and the hydrogenolytic removal of the remaining protective groups furnished the spacer-linked monomer 1 in excellent yield (Scheme 2). Chemical

• synthesis of neo-glycoconjugates Fragments 1–3, obtained as previously reported [25], were employed as follows for the synthesis of the corresponding CRM197 conjugates. First the oligomers 1–3 were activated by reaction with an excess of SIDEA in the presence of triethylamine in DMSO (Scheme 3). The

Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2014, 10, 2307–2321, doi:10.3762/bjoc.10.240

• ][22]. This bears the advantage that the target DNA – the presence or absence of which is going to be analysed – should not be labelled separately with a fluorochrome tag such as cyanine-5 (Cy5) or TAMRA, neither by chemical synthesis nor by a polymerase chain reaction (PCR). The chemical formulae (1–3

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• nucleotides mimicking these alkylation products have been synthesized and then converted into the phosphoamidite building block for chemical DNA synthesis [6][7][18][19][20][21][22][23][24][25][26][27][28]. Not only do these protocols require extensive chemical synthesis, but the sequence of the synthesized

• , without the need of extensive chemical synthesis and with no restrictions with respect to the DNA sequence. The cross-linked analogs of both an A/T and a G/C base pair can be obtained by starting with either an I6S/U4S or G6S/U4S base pair, and therefore, this chemistry can be employed to study any DNA

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• synthesis of 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine (1, clofarabine) were studied. The first approach consists in the chemical synthesis of 2-deoxy-2-fluoro-α-D-arabinofuranose-1-phosphate (12a, 2FAra-1P) via three step conversion of 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-α-D

• formation of the α/β mixtures of N-9 and N-7 glycosides (cf. [17]). Despite the detailed analysis and optimization of the clofarabine process [12][13] and the bulk production of the protected nucleoside glycon 9 by chemists at Eli Lilly and Co. [18] this chemical synthesis is connected with the use of great

• conclusion that the search for novel more efficient “green” methods is of reasonable interest. In this context, the study by Yamada et al. on the chemical synthesis of 2-deoxy-2-fluoro-α-D-arabinofuranose-1-phosphate (12a; 2FAra-1P) and its use in an enzymatic coupling with purine bases is of great interest

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• States 10.3762/bjoc.10.161 Abstract The chemical synthesis of carbacyclopamine analog 2, a cyclopamine analog with an all-carbon E-ring, is reported. The use of C–H-functionalization logic and further metal-catalyzed transformations allows for a concise entry to this new class of acid-stable cyclopamine

• -functionalization logic [11]. In addition, the rational design and chemical synthesis of several analogs and derivatives by this [12][13] and other groups [14][15][16][17] have been disclosed. Here, we report the synthesis of a carbacyclopamine analog (2, Figure 1), an analog of the natural product with an all

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• compounds as references (Scheme 1). Chemical synthesis of the oxidation products In order to identify the biocatalytic oxidation products synthetic routes to compounds 3, 4, 11, 12, 13 and 14 have been developed. The syntheses of compounds 5, 7, 8 [19] and 15–18 [20] have already been described before (see

• -hydroxynerol (4). The chemical synthesis of these compounds requires 3 steps including protection/deprotection of the terminal hydroxy group. Altering regio-, chemo- and stereoselectivity of P450-catalysed reactions remain a challenging task for protein engineering. In the recent years significant achievements

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• intravenous) application, have prompted further research in this field [14]. Therefore, methods to prolong peptide stability are of great interest. Here, we highlight the importance of automated solid-phase peptide synthesis (SPPS) in the process of peptide modification. Principles of chemical synthesis of

• for modulating peptide stability with an emphasis on lipidation and PEGylation are characterized. Last, the syntheses of selected peptide hormones are presented exemplarily. Review Chemical synthesis of peptides and its automation Solid-phase peptide synthesis – the way from homogeneous to

• method simplified the chemical synthesis of peptides and allowed the automation of the process [24], which has led to a breakthrough of SPPS and the establishment as one major technique for therapeutic peptide production [8][19]. Important selections in Fmoc/t-Bu orthogonal protecting-group strategy

Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

• Axel G. Griesbeck and
• Melissa Reckenthäler

Beilstein J. Org. Chem. 2014, 10, 1143–1150, doi:10.3762/bjoc.10.114

• ; photocatalysis; photoredox catalysis; redox; semiconductor; Introduction Stimulated by the principles of sustainable chemical synthesis and the progress in our understanding of catalytic and photoinduced electron-transfer processes, in recent years photoredox catalysis emerged as a new and powerful area for

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• techniques [10][11]. Responsible biochemical transformations are catalyzed usually by enzymes within detoxification processes [12]. Schneweis et al. reported the occurrence of ZEN-14-β,D-glucoside (5, Figure 2A) in wheat [13] and the first chemical synthesis of this compound applying phase transfer

• first chemical synthesis of the ZEN-derivative 14-O-acetylzearalenone (14-AcZEN, produced by some Fusarium strains) [28] is reported. Results and Discussion The general strategy for regiocontrolled conjugation at position 2’ of resorcylic acid esters and lactones is shown in Scheme 1. Regioselective

• successfully used as intermediates for the preparation of corresponding glucosides and sulfates applying the Königs–Knorr glucosylation and chemical sulfation using TCE-protected sulfuryl imidazolium salt 23, respectively. These methods were used for the first chemical synthesis of the ZEN-16-conjugates 7 and

On the mechanism of photocatalytic reactions with eosin Y

• Michal Majek,
• Fabiana Filace and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2014, 10, 981–989, doi:10.3762/bjoc.10.97

• catalysis; quantum yields; visible light; Introduction The ability of natural systems to harness solar energy for the genesis of matter has been fascinating mankind since time immemorial and has stimulated numerous reproduction attempts in the context of chemical synthesis over the last two centuries. The

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• . Besides semisynthetic and total synthesis approaches the combination of chemical synthesis with biotechnological strategies has seen increased interest lately [1][2][3]. The concepts either rely on a concise understanding of the biosynthesis of natural products or simply individual enzymes for in vitro

Convergent synthesis of a tetrasaccharide repeating unit of the O-specific polysaccharide from the cell wall lipopolysaccharide of Azospirillum brasilense strain Sp7

• Pintu Kumar Mandal,
• Debashis Dhara and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2014, 10, 293–299, doi:10.3762/bjoc.10.26

• syntheses facilitate the access to the required tetrasaccharide. A limited number of reports on synthetic studies of the LPS repeating units from the cell wall of Azospirillum are available to date [25][26][27][28][29]. A convenient chemical synthesis of the tetrasaccharide repeating unit corresponding to

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• , antimalarial and antibacterial activity, which are a strong motivation for total synthesis [26][27]. In addition, several ambiguities in the structural assignment of some of these natural products still exist, and chemical synthesis has been proven to be a powerful and reliable tool for completing the

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• , the limited availability of these compounds restricts their potential applications and the chemical synthesis does not satisfy the increasing demand. Izumori et al. created beautiful “Izumoring” schemes displaying all rare sugars in tree form to illustrate possible strategies for the production of

• rare sugars has become a hot topic because of their potential applications in different fields. An important factor restricting the utilization of rare sugars is their limited availabilities, resulting from limited synthetic methods. Biocatalysis often offers advantages over chemical synthesis, because

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• 77030, USA 10.3762/bjoc.9.267 Abstract The chemical synthesis and biological evaluation of new cyclopamine analogs bearing exocyclic methylenes in different positions is described. Bis-exo-cyclopamine 6 was identified as a potent inhibitor of the Gli1-dependent luciferase expression in Shh-LIGHTII

• hampered by its low metabolic stability (decomposition at pH < 3) [31] and rather moderate potency (IC50 ~ 5 µM). We previously reported the first chemical synthesis of cyclopamine (1) starting from dehydroepiandrosterone and utilizing the C–H-functionalization logic and a biomimetic skeleton rearrangement

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• -membered structures will give a comprehensive overview that will be of value to any student, academic or future medicinal chemist interested in applied chemical synthesis. It should be noted that the heterocycles discussed are named according to IUPAC recommendations wherever possible; however, in some

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• as analytical systems [12], multiphase reaction systems [13][14][15], cross coupling reactions [16] and in chemical synthesis of pharmaceutical products [17]. Furthermore, the use of novel process windows to enhance the chemical production has also been reviewed [18][19][20][21][22]. From the

Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

• Hiroyoshi Takamura,
• Takayuki Fujiwara,
• Isao Kadota and
• Daisuke Uemura

Beilstein J. Org. Chem. 2013, 9, 1931–1935, doi:10.3762/bjoc.9.228

• . Therefore, in order to complete the configurational elucidation of 1, we are now investigating its chemical degradation [1][2][3] and chemical synthesis of the fragments [4][5][6][7][8][9][10][11]. Previously, we reported the stereoselective synthesis of the spiroacetal C79–C96 fragment [4], which is

Natural products in synthesis and biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 1897–1898, doi:10.3762/bjoc.9.223

• ] and its further elaboration by chemical synthesis [7] procures sufficient quantities of artemisinin at a reasonable price. An impressive demonstration of the effectiveness of multi-disciplinary research. I would like to thank the highly professional team of the Beilstein-Institut for a very pleasant

Creating Complexity

• Donald Craig

Beilstein J. Org. Chem. 2013, 9, 1881–1882, doi:10.3762/bjoc.9.220

• cyanate could be converted into urea [2]. Since that seminal finding, chemical synthesis has advanced to extents which must have been unimaginable to its early practitioners. The numerous paradigm-shifts which have taken place throughout the history of synthesis have been driven largely by a single

• impulse: the fascination of building sophistication from simplicity – in other words, creating complexity. Chemical synthesis inspires chemists from many different backgrounds, and these scientists are unified in their desire to create and develop methods which enable the creation of complex target

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

• David Benito-Alifonso,
• Rachel A. Jones,
• Anh-Tuan Tran,
• Hannah Woodward,
• Nichola Smith and
• M. Carmen Galan

Beilstein J. Org. Chem. 2013, 9, 1867–1872, doi:10.3762/bjoc.9.218

• , Horsham RH12 5AB, UK 10.3762/bjoc.9.218 Abstract The chemical synthesis of a series of mucin-type oligosaccharide fragments 1–7 containing an α-linked aminopropyl spacer ready for glycoarray attachment is reported. A highly convergent and stereoselective strategy that employs two different orthogonal

Ethyl diazoacetate synthesis in flow

• Mariëlle M. E. Delville,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 1813–1818, doi:10.3762/bjoc.9.211

• chemical synthesis is performed. In particular continuous-flow microreactor technology offers multiple advantages over batch chemistry, including the inherently safe conducting of reactions due to the small reactor dimensions, efficient heat transport and excellent control over the reaction conditions [6

Flow Giese reaction using cyanoborohydride as a radical mediator

• Takahide Fukuyama,
• Takuji Kawamoto,
• Mikako Kobayashi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2013, 9, 1791–1796, doi:10.3762/bjoc.9.208

• access carbon radical species, and they have found numerous applications in chemical synthesis [1][2][3][4][5]. Alkyl radicals are classified as nucleophilic radicals, and therefore they are able to add preferentially to alkenes possessing an electron-withdrawing substituent [6][7]. This type of

• reaction [11][12][13][18] employing this methodology. In Scheme 1, a general mechanism of a borohydride-based Giese reaction with the possible products is shown. In recent years, microreaction technologies have made a significant impact on chemical synthesis and production in terms of their advantageous

Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

• Dinesh Simkhada,
• Huitu Zhang,
• Shogo Mori,
• Howard Williams and
• Coran M. H. Watanabe

Beilstein J. Org. Chem. 2013, 9, 1768–1773, doi:10.3762/bjoc.9.205

• compound as dimethyl furan-2,4-dicarboxylate, which has been previously observed in microbial head-space or vapor phase extracts and its structure determined through chemical synthesis [15]. The biosynthetic origin of dimethyl furan-2,4-dicarboxylate could be polyketide derived where the furan ring system