New tris- and pentakis-fused donors containing extended tetrathiafulvalenes: New positive electrode materials for rechargeable batteries

• Shintaro Iwamoto,
• Yuu Inatomi,
• Daisuke Ogi,
• Satoshi Shibayama,
• Yukiko Murakami,
• Minami Kato,
• Kazuyuki Takahashi,
• Kazuyoshi Tanaka,
• Nobuhiko Hojo and
• Yohji Misaki

Beilstein J. Org. Chem. 2015, 11, 1136–1147, doi:10.3762/bjoc.11.128

• value is also superior to the energy densities of most inorganic cathode materials for LIBs [29][30], 20/Li (605 mWh g−1) [31], and is slightly smaller than that of 21/Li (700 mWh g−1) [32] (Figure 9). Conclusion A TTF derivative with two phosphonate groups (12) is a useful building block for the

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• cycloaddition (CuAAC) [25][26] has naturally inspired the use of this powerful conjugation method to prepare glycan–DNA conjugates. Chevolot and co-workers used this method to conjugate glycans at the 3’-end of DNA [27]. The DNA synthesis was initiated with H-phosphonate that was converted to a phosphoramidate

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• natural nucleobases with unnaturally-substituted heteroaromatics or homoaromatic systems, or the modification of the phosphate P(O)–O–C bond with the non–hydrolyzable phosphonate P(O)–C linkage [17][18]. In this context, nucleoside analogues, where different carbon or heterocyclic systems replace the

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• known [44][45], deoxygenation of the functionally much more complex phosphonate 3b to the dinucleoside analog of 1 was not attempted. Only one example of an acylphosphonite analog of 1 was found in the literature, namely, a dinucleoside formate reported by Caruthers et al. [46]. As shown in Scheme 1

• of the structures was possible via oxidation and conversion to the known diastereomeric phosphorothioates. As shown by Hata et al., acylphosphonate 3b (Scheme 1) was converted to the corresponding phosphorothioate by treatment with a base (to give the H-phosphonate via loss of carboxylate) followed

• by elemental sulfur [43]. As shown in Scheme 3, oxidation of 12 and 13 with anhydrous tert-butyl hydroperoxide gave the acylphosphonates 14 and 15. These products were immediately hydrolyzed by addition of approximately 2 equiv of aqueous triethylammonium bicarbonate (TEAB) to give the H-phosphonate

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• reactions with glycine-derived phosphonate 12 and to compare both possible routes towards 9, i.e., with or without thymine protection (Scheme 1). For the synthesis of the N-Fmoc-protected thymidine-derived nucleosyl amino acids (S)-9 and (R)-9, 3',5'-bis-O-silylated thymidine 13 (which can be readily

• stability, thymidine-5'-aldehydes 10 and 11 were not stored, but directly used for the subsequent Wittig–Horner reaction. They were therefore converted with glycine-derived phosphonate 12 [51][52][53][54] in the presence of potassium tert-butoxide as a base. As anticipated [47][48][55], these reactions

• showed pronounced stereoselectivity towards the Z-configured didehydro nucleosyl amino acids. In the case of the reaction of 3-(N-BOM)-protected thymidine-5'-aldehyde 10 with phosphonate 12, isomer Z-17 was isolated in 71% yield, with E-17 representing a minor byproduct (3% yield) which could be

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• chromatography. Chlorinated AHL analogues 11a–f were prepared via a one pot procedure (Scheme 3). In this route the acylphosphonates 9a–f were prepared by an Arbuzov reaction and were subsequently chlorinated via reaction with sulfuryl chloride [29][30]. The phosphonate function is used as a strong activating

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

• by the in vitro bactericidal assay recently developed for the evaluation of MenX CPS conjugates [18]. Results and Discussion Improvements in α-H-phosphonate synthesis Our previous synthesis of oligomers 1–3 featured the use of 2-azido-2-deoxy glucopyranosyl building blocks and their corresponding

• , when the hemiacetal 6 was treated with salicylchlorophosphite in pyridine at room temperature the α-H-phosphonate 7 was obtained as a single anomer in only 2 h in 62% yield. We reasoned that the occurrence of an intramolecular hydrogen bond involving the acetamido group could be the main responsible

• for the high selectivity observed in the formation of compound 6 and, consequently, for the attainment of the pure α-H-phosphonate 7. Indeed, the desilylation of the 2-azido counterpart of intermediate 5 provided a mixture of anomers. On the other hand, the same reaction carried out on a 2-acetamido

Solution phase synthesis of short oligoribonucleotides on a precipitative tetrapodal support

• Alejandro Gimenez Molina,
• Amit M. Jabgunde,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2014, 10, 2279–2285, doi:10.3762/bjoc.10.237

• solution phase approach, allowing assembly of short RNAs in a hundreds of milligrams scale. While several such methods for the synthesis of DNA, based either the phosphoramidite [11][12][13][14][15][16], H-phosphonate [17][18][19] or phosphotriester chemistry [20][21][22], have been introduced, none of

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• , nucleosides and nucleobases play an important role in all biological systems. Therefore, it is not surprising that many of their analogs possess interesting biological properties. Potent antiviral drugs based on phosphonate nucleotides 1a–c [1][2], 2a–d and 3a–d (Figure 1) have been reported. Prodrugs of

• successful approach in developing antiviral therapeutics. Our long-term interest in the synthesis and evaluation of biological properties of phosphonate azanucleotides has yielded several potent inhibitors of nucleoside/nucleotide metabolizing enzymes: thymine derivatives 4 and 11 (Figure 1 and Figure 2

• analogs [12]. In this publication, we present a conformational analysis of pyrrolidine azanucleotide analogs 7–14 containing thymine and adenine as examples of pyrimidine and purine nucleobases, respectively (Figure 2), and show how the conformation is affected by the mode of the phosphonate moiety

Relay cross metathesis reactions of vinylphosphonates

• Raj K. Malla,
• Jeremy N. Ridenour and
• Christopher D. Spilling

Beilstein J. Org. Chem. 2014, 10, 1933–1941, doi:10.3762/bjoc.10.201

• phosphorus; relay; vinyl phosphonate; Introduction Over the last two decades, we have developed reactions for the formation of chiral non-racemic γ-substituted vinylphosphonates [1][2][3][4][5][6][7][8][9]. In particular, carbonate derivatives 1 (phosphono allylic carbonates) of allylic hydroxy phosphonates

• turmerone [4] and enterolactone [5], the phosphonate derivatives of the natural product cyclophostin [6], the C18–C34 fragment of amphidinolide C [7], and the oxylipids from Australian brown algae [8]. The potential of vinylphosphonates as intermediates in organic synthesis is limited by their chemistry

• ]. Therefore, given the propensity for vinylphosphonates to undergo RCM, it was proposed that an allyl phosphonate ester 14 would act as an initial site of metathesis, which would lead to a relay cross metathesis and thus render vinylphosphonates reactive. Results and Discussion A series of cross metathesis

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• inseparable by normal chromatographic methods. The chiral backbone of 77 had a beneficial effect on the stereoselectivity of the olefination, with an improved E/Z ratio of 91:9 compared to the achiral analogue 24e (Table 1, entries 1 and 2). Employing phosphonate-Weinreb amide 78 and phosphonamide-Weinreb

Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase

• Xiang Zhou,
• Jacqueline E. Reilly,
• Kathleen A. Loerch,
• Raymond J. Hohl and
• David F. Wiemer

Beilstein J. Org. Chem. 2014, 10, 1645–1650, doi:10.3762/bjoc.10.171

• no activity against FDPS even at a 10 μM concentration. Keywords: bisphosphonate; isoprenoid biosynthesis; organophosphorous; phosphonate formation; Introduction Several enzymes of the isoprenoid biosynthesis pathways are the targets of widely prescribed drugs. For example, hydroxymethylglutaryl

• alkoxide after formation of the bisphosphonate would face the strong possibility of phosphonate–phosphate rearrangement [15][16][17]. However, diethyl hydroxymethylphosphonate (7, Scheme 1) is known to react with a base and geranyl bromide to afford the ether 8 in good yield [18]. With compound 8 in hand

• dialkyl bisphosphonate 5, and gave the desired tetraethyl O,C-digeranylbisphosphonate 10. Hydrolysis of the phosphonate esters proceeded under standard McKenna conditions [24], but only a limited amount of the product 6 was recovered after precipitation from acetone/water. A parallel hydrolysis of

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• Zbigniew Pakulski Norbert Gajda Magdalena Jawiczuk Jadwiga Frelek Piotr Cmoch Slawomir Jarosz Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland 10.3762/bjoc.10.124 Abstract The reaction of appropriately functionalized sucrose phosphonate with

• shown in Figure 2. The properly activated sugar is converted into phosphorane or phosphonate which – upon reaction with an aldehyde derived from another monosaccharide – provides higher carbon sugar (HCS) enone [16][17][18]. Application of this methodology to selectively protected 2,3,3’,4,4’-penta-O

• the ‘fructose end’ providing alcohol 6 [8]. This alcohol was converted into aldehyde 7 [21] (route a in Scheme 1) and separately into phosphonate 9 (route b). Reaction of both synthons under the mild PTC conditions [22][23][24] afforded the respective enone 10 in good yield (Scheme 1

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• phosphite as a substrate. This result might be rationalized by the instability of trichloromethanide in aprotic media which in the presence of dimethyl phosphite or dimethyl chlorophosphate produced a significant amount of carbene. It must be mentioned that methyl esters of phosphate or phosphonate have a

• phosphate group reacted with aryl Grignard, as a Kumada–Tamao-Corriu cross-coupling, in the presence of a nickel catalyst [90]. Aryl dialkyl phosphate, which was readily obtained by the AT reaction from phenol as shown in Scheme 31 [91], can be employed for the production of aryl phosphonate by applying a

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• , entry 2), a tosylate leaving group (Table 1, entry 4), and a halide (Table 1, entry 5). Somewhat more exotic functional groups such as a phosphonate ester (Table 1, entry 6) or a dimethyl acetal (Table 1, entry 7) were still tolerated in the reaction, albeit in more modest yields. A variety of alkylated

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

• skeleton and a phosphorus atom. For the C9 ketones a phosphonate–phosphate rearrangement, associated with a tandem elimination of the piperidine fragment, was evidenced. Keywords: carbonyl derivatives; dialkyl phosphite addition; organophosporus; phosphonate–phosphate rearrangement; quinine oxidation

• chromatography, for details see Supporting Information File 1). C9 position modification, phosphonate–phosphate rearrangement Oxidation of the C9 hydroxy group of quinine to the corresponding ketone, quininone, was performed with potassium tert-butoxide and benzophenone (Scheme 4) [34]. Using toluene as the

• typical for phosphates, 13b: −5.76 and −5.49 ppm. Apparently, they were products of the phosphonate–phosphate rearrangement of intermediate hydroxyphosphonates [36][37][38]. Treatment of ketones 11 and 12 with dimethyl- and diphenyl phosphite brought quite similar results. The expected product, diphenyl

Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• aldehyde 21 with the anion of diethyl [(2E)-3-methoxycarbonyl-1-methyl-2-en-1-yl]phosphonate, followed by reduction of the resulting methyl ester (Figure 4). The obtained product proved to be a mixture of 23 and its (2E,4Z)-isomer (23a) in a ratio of about 1:1. For an unambiguous gas-chromatographic

• -2-en-1-yl]triphenylphosphonium bromide, n-BuLi, LiBr, THF, −40 °C, 12 h; i: 1) diethyl [(1/2EZ)-3-(methoxycarbonyl)-1-methylprop-1/2-en-1-yl]phosphonate (as a mixture of isomers [23]), NaHMDS, LiBr, THF, −90 °C, 1 h; 2) 21, −70 °C to rt, 16 h; j: DIBAlH, DCM, −80 °C to rt, 2.5 h. Supporting

Synthesis of fluorescent (benzyloxycarbonylamino)(aryl)methylphosphonates

• Michał Górny vel Górniak,
• Anna Czernicka,
• Piotr Młynarz,
• Waldemar Balcerzak and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 741–745, doi:10.3762/bjoc.10.68

• carrying fluorescent probes in their side chains or in the ester phosphonate moieties might find an application in constructing fluorescent probes for studying structural requirements of enzymes having serine in their active sites (proteinases and phosphatases) or to study their elevated level in various

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• formaldehyde, forming (α-hydroxymethyl)phosphinate 8. Its further irreversible rearrangement [28] to the corresponding phosphonate 9 was accompanied with hydrolysis of the ester function and formation of (trifluoromethyl)phosphonic acid (10) [29] as the main product. Analogous results were obtained, when CHF2

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• assay mixture, the latter will be transformed into their corresponding methyl esters by saponification and following methylation with trimethylsilyldiazomethane. The fully protected E-isomer 10a was obtained in 18% yield by a Horner–Wadsworth–Emmons reaction with phosphonate 25 or, alternatively, in 64

• % yield by a Wittig reaction with stabilized phosphorane 26. The Z-isomer 10b was synthesized by Still–Gennari olefination using phosphonate 27 in 47% yield. The yield for the deprotection step was satisfying (61% for 7a and 57% for 7b) in both cases, indicating that both isomers are configurationally

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• % CuIP(OEt)3 and phenyl propargyl ether as the alkyne provided triazole-peptidomimetics 85 in 70–80% yield (Scheme 26). In a follow-up publication the same authors reported the development of tetrapeptides bearing α-CF3-α-amino and α-CF3-α-amino phosphonate cores (Scheme 27) [86]. Fluorinated compounds

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• –Emmons reaction (HWE). The HWE reaction has many advantages over the Wittig olefination. The phosphonate anions tend to be more nucleophilic (less basic) than the corresponding phosphorous ylides. The byproducts, dialkyl phosphates are water soluble and hence easier to remove from the product compared to

• the phosphonate makes the synthesis of Z-enoates possible [115]. The two electron-withdrawing CF3CH2O-groups destabilize the cis-oxaphosphetane intermediate (Scheme 27) and make the elimination reaction to the kinetic product Z-alkene a lot faster. As the elimination step becomes fast, the rate

• recently shown that the open-chain aldehyde 74 reacts with the Still–Gennari phosphonate and provides the Z-enoate 75 in good E/Z-selectivity (1:12) [84]. The slight decrease in the E/Z-selectivity can be reasoned with the smaller size of the aldehyde 74. When the aldehyde is coordinating to the

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

• became accessible. Partial reduction to the lactol (DIBAl-H, THF, −78 °C to −65 °C, 88%) and Horner–Wadsworth–Emmons reaction by using previously reported dimethyl {3-[(4-methoxybenzyl)oxy]-2-oxopropyl}phosphonate [32], (Ba(OH)2, THF/H2O, 80 °C, 50%) led to 15 which, in turn, was methylenated by

• -methoxybenzyl)oxy)-2-oxopropyl)phosphonate, Ba(OH)2, THF/H2O, 80 °C, 13 h, 50%; (i) (trimethylsilyl)methylcerium chloride, THF, −78 °C, 30 min; then TMEDA, −78 °C, 15 min; then HF 50 wt % in H2O, MeCN, 25 °C, 10 min, 64%; (j) LiAlH4, THF, 0 °C→25 °C, 13 h; then benzenesulfonyl chloride, Et3N, DMF, 0 °C, 25 min

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

• olefination. Installation of the phosphonate and desilylation gave 76, which, after oxidation, reacted in the presence of sodium 2,2,2-trifluoroethanol (NaOTFE) in 2,2,2-trifluoroethanol (TFE) via an intramolecular Horner–Wadsworth–Emmons reaction to 77. Cytochalasin L-696,474 (78) was obtained from 77 via

Synthesis and quantitative structure–activity relationship study of substituted imidazophosphor ester based tetrazolo[1,5-b]pyridazines as antinociceptive/anti-inflammatory agents

• Wafaa M. Abdou,
• Neven A. Ganoub and
• Eman Sabry

Beilstein J. Org. Chem. 2013, 9, 1730–1736, doi:10.3762/bjoc.9.199

• . Bucolome) [24]. Several phosphonate derivatives also exhibit marked potency as inhibitors of COX-1 and COX-2 and are therefore believed to be useful as anti-inflammatory drugs [25][26]. Thus, we considered that it is of interest to gather these three motifs in one molecule. Results and Discussion It has

• carbanion 2a or 2b on the azido-function in 1b yielding the phosphonate intermediate 3 along with the evolution of a nitrogen molecule. Subsequent intramolecular ring closure, the fused imidazolo-phosphonate 4 would be obtained under elimination of an appropriate alcohol moiety. In the same fashion, the

• substrate 1b reacted with the phosphonyl carbanion, diethyl cyanomethylphosphonate 5, in ethanolate solution to yield diethyl 8-aminoimidazo[1,2-f]tetrazolo[1,5-b]pyridazin-7-ylphosphonate (7) in 74% yield. The IR spectrum of the phosphonate 7 (δP = 27.8 ppm) showed the NH2, P=O, and P–O–C motifs at ν 3377