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

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• chemical synthesis, guided by GIAO chemical shift prediction, is currently underway in an effort to elucidate the correct structure for piperazirum. In addition the determination of further biological activity of 2 and its diastereoisomers will be investigated. Experimental Unless otherwise stated, all

Chemistry in flow systems III

• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1696–1697, doi:10.3762/bjoc.9.193

• chemical synthesis in the laboratory from a classical batch approach to continuous processes by using micro- and miniaturized flow reactors. In the past two decades this technology has seen a dramatic increase of visibility. Considering an analyses of the accompanied developments in flow synthesis one has

• synthetic examples. The combined work of experts from engineering and chemical synthesis was highly fruitful and is so until today. This combination of expertise has catalyzed the development of microreactor technology in the applied context of synthesis and production. Chemical engineers depend on input

The rapid generation of isothiocyanates in flow

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 1613–1619, doi:10.3762/bjoc.9.184

• chemical transformation which typically eliminates the requirements for any conventional work-up or purification of the reaction stream. Keywords: chloroxime; dipolar cycloaddition; flow chemistry; flow synthesis; immobilised reagents; isothiocyanate; nitrile oxide; Introduction Flow based chemical

• synthesis is playing an increasingly pivotal role within the chemical sciences as it facilitates a more versatile and responsive workflow. It encompasses many aspects of synthesis from the rapid and on-demand preparation of important building blocks to the development of multi-step sequences leading to

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• algorithms, camera-enabled apparatus can perform some of these processes in an automated fashion, allowing skilled chemists to spend their time more productively. In this review we describe recent advances in this field of chemical synthesis and discuss how they will lead to advanced synthesis laboratories

• efficient use of space and the opportunity for a 24/7 working regime, the ability of digital cameras to provide real-time information on the state of a laboratory is particularly useful. When we established our Innovative Technology Centre (ITC) for advanced chemical synthesis in 2005, all of the fume-hoods

• and control, which will be of great benefit to the scientific community. Machine-assisted procedures can benefit from improved reproducibility and more detailed collection and reporting of data throughout a chemical synthesis. The evolution of computer-based monitoring and control within the

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• ; diversity-oriented synthesis; metathesis; Introduction Our collective understanding of the biological relevance of chemical space has been shaped, in large part, by the historic exploration of chemical space by chemical synthesis (and biosynthesis) [1]. The scaffolds of known bioactive small molecules, in