Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• , compound 1 was subjected to carbonyl reduction which occurred with high stereoselectivity from the less hindered, convex side of the bicyclic system, resulting in alcohol 2 along with traces of its epimer. To increase the stereoselectivity of the upcoming cyclopropanation reaction it seemed appropriate to

• structures (right); bottom row: tc-T (Mol A, left, Mol B, right). Conditions: (a) NaBH4, CeCl3·7H2O, MeOH, −78 °C → rt, 1.5 h, 73% (+9% of C6-epimer); (b) TBS-Cl, imidazole, CH2Cl2, rt, 16 h, 79%; (c) Et2Zn in hexane (1 M), CH2I2, CH2Cl2, 0 °C → rt, 16 h, 86%; (d) PivCl, DMAP, pyridine, ClH2C–CH2Cl, 70 °C

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• its epimer (Scheme 21) [87]. After completion of the synthesis of the urea dipeptide 53 bearing the cyclic moiety found in muraymycin D2, the four-component condensation was performed similarly as in [86] to yield the protected product 54 as a 1:1 diastereomeric mixture. Functional group manipulation

•  22) [89]. The urea dipeptide 55, 2,4-dimethoxybenzylamine, the protected (S)-2-(methylamino)propanal, and isonitrile 56 were simply combined in ethanol at ambient temperature for 48 h. The expected compound 57 and its epimer were obtained in reasonable yields, and were separated by column

• chromatography. The syntheses of 3′-hydroxypacidamycin D and its epimer were then accomplished in four steps from intermediates 57 or epi-57, including selective deprotection of the N-methyl-Boc group, coupling with N-Boc-L-alanine, and global deprotection. This strategy was also applicable to the synthesis of a

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• or its epimer rhodinose, respectively [33]. An approach to amicetose (and a few other 6-desoxy sugars) involves the formation of an enantiopure β,γ-unsaturated δ-valerolactone via ring closing metathesis (RCM). The RCM product is subsequently converted into L-amicetose in four steps [34

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• acid using Fmoc N-hydroxysuccinimidyl carbonate (Fmoc-OSu) under basic conditions gave sugar β-amino acid Fmoc-L-glycero-glucose(Bn)-OH 12a in 81% yield (Scheme 1). The C6-epimer Fmoc-D-glycero-glucose(Bn)-OH 12b was obtained by analogous procedures as performed for 12a. The synthesis of Fmoc-D-glycero

Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination

• Łukasz Górecki,
• Artur Mucha and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 883–889, doi:10.3762/bjoc.10.85

• cleavage on silica in a two-phase system led predominantly to the C3 epimer of the R configuration 90:10 (yield 93%) in a short reaction time [27]. In our case, when the reaction time was prolonged to 2 hours, the overall yield remained at the same level while the diastereoselectivity was reduced to 71:29

• varied in the range of 40–50% (Scheme 3). The R-C3 epimer gave rise to somewhat more pronounced induction. The 31P NMR resonances of the predominating forms of the hydroxyphosphonate are shifted apart by approximately 1.0 ppm. We speculate that this means a diastereomeric relationship of their C3–C10

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• epimer of monensin A at C-9 [17] has provided clear evidence that both MonD and MonE are capable of acting on altered substrates, which is encouraging for future engineering experiments aimed at production of novel derivatives. To help to provide a platform for such experiments, and to further elucidate

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• . There are also other, enantioselective syntheses of 7 [7] and Boc-protected versions of MMMAH [8][9], but we intended to also have the (3S)-epimer of 7 at our disposal. After hydrogenation of 7, the resulting secondary amine was coupled with Cbz-valine (8) affording dipeptide 9 (DEPCl, diethyl

Decandrinin, an unprecedented C₉-spiro-fused 7,8-seco-ent-abietane from the Godavari mangrove Ceriops decandra

• Hui Wang,
• Min-Yi Li,
• Félix Zongwe Katele,
• Tirumani Satyanandamurty,
• Jun Wu and
• Gerhard Bringmann

Beilstein J. Org. Chem. 2014, 10, 276–281, doi:10.3762/bjoc.10.23

• decandrinin (1), NOE interactions for the B97D/TZVP-optimized structure diagnostic for the 9-epimer of decandrinin (1), and comparison of the calculated ORD with the experimental one. Acknowledgements This work was financially supported by NSFC (31100258, 31170331, and 81125022), the Guangdong Key Science

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• epimer (R)-5 and the 9-epi-amino derivatives (R)-6/7a–f give unexpectedly complex 1H/31P NMR spectra in CDCl3/DMSO-d6 at room temperature. Signals that belong to any one proton split into two signals with a ratio of ~5:1/20:1 depending on the solvent. The reason for this is conformational isomerism

• quinine, gives modest yields (60%) albeit with low enantiomeric excess (13% ee). Lowering the reaction temperature with catalyst 4 results in a slightly higher enantiomeric excess (27% ee, Table 2), however the yield drops to only 30%. We anticipated an increase in enantioselectivity for the epimer 5 as

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• both good yield and good diastereomeric ratio. Selective hydrogenation of the more electron rich double bond followed by reduction of the ester furnished α,β-unsaturated ketone 104 after PPTS-catalyzed elimination of water. Subsequent DIBAL-H reduction yielded the alcohol epimer 105 of barekol (107

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• , Boston, MA 02215, United States 10.3762/bjoc.9.296 Abstract We completed a new and efficient synthesis of D-chalcose (I) and the first synthesis of its C-3 epimer (I′) in nine steps with overall yields of 23% and 24%, respectively. The key steps in the sequence were the formation of the stereocenter on

• -10-camphorsulfonic acid (CSA) in MeOH. Keywords: asymmetric dihydroxylation; chalcose; epimer; total synthesis; Introduction Chalcose (4,6-dideoxy-3-O-methyl-D-xylo-hexose, I [1][2]) is a structural component of many macrolide antibiotics, such as chalcomycin [3], neutramycin [4], and lankamycin [5

• new and efficient 9-step synthesis of D-chalcose (I) with a 23% overall yield. In addition its efficiency, the route enabled facile preparation of chalcose’s C-3 epimer (4,6-dideoxy-3-O-methyl-D-ribo-hexose, I′); the C-3 epimer has not been synthesized previously. Results and Discussion The

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• biological activities (Scheme 2). Results and Discussion Synthesis of racemic jaspine B and its C-2-epimer Initial studies examined the feasibility of this planned approach for the generation of the functionalized tetrahydrofuran system. They were based on methoxyallene (5) and led to the preparation of the

• reduction of carbonyl compounds bearing an electronegative group in α-position [37]. After palladium-catalyzed hydrogenolysis of α-azidotetrahydrofuranols rac-9 and rac-10 an inseparable mixture of racemic jaspine B (rac-1) and its C-2-epimer rac-2 was obtained. Hence the natural product and its

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

• -Psicose is a C-3 epimer of D-fructose and a potential sucrose substitute sweetening agent. The suppression of hepatic lipogenic enzymes activity of D-psicose has been noticed for its use as a non-caloric sweetener [25][26]. In addition, antioxidant properties have been observed for foods containing this

• -rhamnitol) which was subsequently oxidized by Enterobacter aerogenes IK7 to afford the rare sugar 1-deoxy-L-fructose. The whole process was performed in an environmentally friendly fashion. II. Biosynthesis of rare aldohexoses D-Allose D-Allose is the C-3 epimer of D-glucose or the aldo/keto-isomer of D

• oxygen. L-Talose and D-gulose The aldohexoses L-talose and D-gulose (C-3 epimer of D-galactose) are both very expensive owing to their scarcity in nature. L-Talofuranosyladenine, an adenine nucleoside derivative of L-talose, was found to be a slow-reacting substrate for calf intestinal adenosine

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• submitted to different transformations. For example, it could be reduced to the corresponding pyrrolidines employing sodium cyanoborohydride in acidic media. In this reaction, a 1:1 mixture of 2,5-cis-pyrrolidine 13 and its 5-epimer 14 (2,5-trans) was isolated in good chemical yield (71%) (Scheme 7

• , reaction a). Fortunately, 5-epimer 14 (2,5-trans) was diastereoselectively generated through a 10% Pd/C-catalyzed hydrogenation using 4 atmospheres of hydrogen during three days at 25 °C (Scheme 7, reaction b). This trans- arrangement in molecule 14 is not very easy to built because several steps were

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• as an advanced intermediate for the synthesis of pumiliotoxin 251D [12]. Later on, Nubbemeyer and co-workers used the Horner olefination to convert 5 and its diastereomer into (+)-PTX 251D (2) and the 8-epimer of PTX 209F (4), respectively [17]. Recently, (8S,8aS)-5 has been used for the synthesis of

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

• catalyst in benzene yielded previously described exo-cyclopamine 2 and its C25 epimer 5. Deprotection with Raney-nickel (EtOH, 78 °C) and then sodium naphthalenide (DME, −78 °C, 41% over two steps) furnished 25-epi-exo-cyclopamine 5 in 3% overall yield from 3. A first set of exo-cyclopamine analogs with a

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• for this system. The stereochemical outcome could be attributed to the sterically less demanding transition state 82b. The epimerization of 83 to 85 proceeded via an intermediate lactone and extended the route by seven steps. After having secured the cis-epimer 85, the diene moiety was introduced in

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• alkene geometry was determined to be (2E,5E,8E) by measurement of NOE enhancements [4]. Ripostatin B and its C15 epimer can be obtained from ripostatin A by reduction with sodium borohydride, while ripostatin C can be formed from ripostatin A by a mild base-mediated elimination. Consequently, ripostatin

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• same relative position in space [48][49]. Peptidomimetic negative modulators of the D2 dopamine receptor Biological evaluation of the C-8’a epimer of the type II β-turn PLG peptidomimetic 29a, spiro-bicyclic 29b, and of the C-8’a epimer of the polyproline II helix PLG peptidomimetic 49a, spiro-bicyclic

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

• Katharina Gallas,
• Gerit Pototschnig,
• Florian Adanitsch,
• Arnold E. Stütz and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2012, 8, 1619–1629, doi:10.3762/bjoc.8.185

• corresponding acetals when the pH value is kept below 6 [30]. In the D-gluco series, D-glycero-D-gulo-aldoheptose 10 was isolated in 81% yield, and no C-2 epimer was detected, as shown by comparison of the NMR data with a commercial sample [31]. Aldoheptose 10 was taken to the Amadori rearrangement without

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• of the crude peptide, so obtained, to authentic samples of both 5 and the C-terminal epimer 9 (which was independently prepared by solid-phase peptide synthesis), indicated that the major product obtained upon macrolactonization of 5 under the Corey–Nicolaou conditions was the undesired cyclic

• the desired cyclic depsipeptide 7 (58% isolated yield, with 5–12% of epimer 8 also observed) were obtained using a modification of Yonemitsu’s conditions [23] in which linear peptide 5 was added slowly to a solution of DMAP, 2,4,6-trichlorobenzoyl chloride and triethylamine in toluene at room

• temperature. Similar yields and low epimerization (52% isolated yield, 6% epimer observed) were obtained using 2-methyl-6-nitrobenzoic anhydride (MNBA) [24] as the activating agent in place of 2,4,6-trichlorobenzoyl chloride. To investigate whether the ΨMe,Me'Pro would assist macrolactonization, linear

On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• strategy for controlling the stereochemistry of oxygenated 5,5-spiroketals. The same strategy likewise enables the first stereocontrolled synthesis of cephalosporolide E, which is typically isolated and prepared admixed with its spiroketal epimer, cephalosporolide F. Keywords: cephalosporolides; chelation

• -spiroketals 21a and 21b was obtained in 71% overall yield from 20. The mixture of diols 21a and 21b converged to 21a (epimer 21b no longer observable by 1H NMR) upon treatment with zinc chloride. TEMPO oxidation of diol 21a led to the formation of cephalosporolide E (2, admixed with a minor diastereomer

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part II: Iridomyrmecins

• Robert Hilgraf,
• Nicole Zimmermann,
• Lutz Lehmann,
• Armin Tröger and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1256–1264, doi:10.3762/bjoc.8.141

• and Y are strictly opposite, whereas the relations between X and Z are relatively close, showing inversion at C-4 only. Strangely, Z is not the expected C-4-epimer of Y, but the C-4-epimer of its enantiomer. Apart from very few exceptions such as methoxymyodesertene (24) [41], the 4-nor-nepetalactone

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• , over Pd/C (10%) to give a 9:1 mixture of the all-cis versus the all-trans product [29]. In our case, the application of Lange’s method to the aldehyde 23 led to the formation of a 3:1 mixture of the all-cis versus the all-trans epimer. Subsequent treatment with sodium methoxide in MeOH at rt for 20 h

• acetate 26 was oxidized to the aldehyde 30, which could be epimerized using p-toluenesulfonic acid in benzene under reflux conditions to provide a 2:3 mixture of the desired aldehydes 30 and its epimer 30*. Subsequent steps were carried out with the mixture of diastereomers. Reaction of 30/30* with sodium

Enantioselective supramolecular devices in the gas phase. Resorcin[4]arene as a model system

• Caterina Fraschetti,
• Matthias C. Letzel,
• Antonello Filippi,
• Maurizio Speranza and
• Jochen Mattay

Beilstein J. Org. Chem. 2012, 8, 539–550, doi:10.3762/bjoc.8.62

• ’-deoxycytidine dC, cytidine, Cy, cytarabine CT, an epimer of cytidine, and gemcitabine GC, which is the gem-difluoro derivative of 2’-deoxycytidine (Figure 8). Two reaction products were observed in the reaction with the enantiomers (2)-aminobutane: the addition [M·H·G·B]+ and the ligand-exchange [M·H·B