Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• –Wadsworth–Emmons (H.W.E.) reaction of n-hexanal with phosphonoester 19 [15] afforded an E/Z mixture of olefinic diesters, purification of which by silica gel column chromatography afforded a fraction of the desired E diester 20 (60%), a second fraction comprised of a 5:1 E/Z mixture and a third fraction of

• Z diester 21 (10%, Scheme 3). The reduction of diesters 20 (E) and 21 (Z) with LiAlH4 afforded diols 22 and 23 in 63% and 67% yield, respectively. Subsequent oxidation of 22 with DMP afforded dialdehyde 11 in 31% yield. Correspondingly, the reaction of diol 23 with DMP afforded a mixture of

• to onchidal (6) were attempted. H.W.E reaction of 2-cyclohexylacetaldehyde (24) [16] with phosphonoester 19 afforded a fraction of the desired E diester 25 in 15% yield, a fraction of Z diester 26 in 1.5% yield and another fraction of a mixture of the two (5:1) (Scheme 4). The reaction of diesters 25

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• moderate water solubility and peptide-like folding properties [9] are hurdles for their biological application. As an alternative strategy, the (deoxy)ribose part of the backbone has been retained and only some of the internucleotide phosphate diesters have been selectively replaced by electroneutral

• backbone phosphate diesters, the term 'DNmts' was coined. Just like the guanidinium linkage in DNGs, the S-methylthiourea modification is not stereogenic and stable towards nuclease-mediated cleavage. Furthermore, it retains its positive charge independent of pH conditions. Bruice and co-workers initially

An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

• Gernot A. Eller,
• Gytė Vilkauskaitė,
• Algirdas Šačkus,
• Vytas Martynaitis,
• Ashenafi Damtew Mamuye,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2018, 14, 1287–1292, doi:10.3762/bjoc.14.110

• of 5-hydroxypyrazole-4-carboxylates in refluxing thionyl chloride. The obtained diesters can be transformed into the corresponding 4,4'-bipyrazoles via alkaline hydrolysis and subsequent decarboxylation. Detailed NMR spectroscopic investigations (1H, 13C, 15N) were undertaken with all products

Polysubstituted ferrocenes as tunable redox mediators

• Sven D. Waniek,
• Jan Klett,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2018, 14, 1004–1015, doi:10.3762/bjoc.14.86

• . Mono-, 1,1’-diesters and a single 1,1’,3-triester of ferrocene are known [45][46][47][48][49][50][51][52][53]. Elegant routes to 1,1’,3-tris(methoxycarbonyl)ferrocene and 1,1’,3,3’-tetrakis(methoxycarbonyl)ferrocene were developed only very recently [54], complementing the series of methyl esters of

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• Satu Mikkola Tuomas Lonnberg Harri Lonnberg Department of Chemistry, University of Turku, FIN-20014 Turku, Finland 10.3762/bjoc.14.68 Abstract Nucleic acids that store and transfer biological information are polymeric diesters of phosphoric acid. Cleavage of the phosphodiester linkages by protein

• studies with small molecular phosphodiesters. Keywords: Cleavage; DNA; kinetics; mechanism; RNA; Introduction Nucleic acids are polymeric diesters of phosphoric acid that store and transfer biological information. In biological systems, the diester linkages bridging 3´-O of one nucleoside to the 5´-O of

• fission of the intermediate to a 2´,3´-cyclic phosphate, leading to pH-independent cleavage, is much slower (Scheme 1). The rate of this reaction (black line in Figure 6) is only 2% of the interconversion rate of 2´,5´- and 3´,5´-diesters [44]. Studies with various uridine 3´-alkylphosphates have, however

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• phosphorothioate diesters from the fma thiophosphate triesters with a thermolytic conversion half-life of t1/2 = 73 h at 37 °C. Although these fma ODNs exhibit the features of ON prodrugs in that they are neutral to enable cellular delivery and are stable to hydrolytic nucleases, Beaucage et al. developed other

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• tetraoxaadamantanes 20–25 took place (Scheme 6) [29]. The reaction is usually carried out at room temperature in dichloromethane in the presence of concentrated HCl and glacial acetic acid, and the yields are mostly in the range 65–95%. Depending on the starting material, diesters, monoesters or the fully

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• with acyl chlorides or chlorophosphates [11][12][13]. On applying the phosphoramidite chemistry, the phosphite triesters obtained are oxidized to phosphate triesters in each coupling cycle, whereas the H-phosphonate diesters may be stable enough to become oxidized only at the end of chain assembly

• . When the coupling is carried out at P(V) level, 3´-arylphosphate diesters (3 in Scheme 1) are normally used as building blocks and activated with arylsulfonyl chloride or azolide in the presence of an auxiliary nucleophilic catalyst [14], or a catalytically active phosphate protecting group, such as

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• , Australia 10.3762/bjoc.13.133 Abstract Background: Croton oil is the only commercial source of the diterpenoid phorbol (1a), the starting material for the semi-synthesis of various diesters extensively used in biomedical research to investigate cell function and to evaluate in vivo anti-inflammatory

• by Berenblum in 1941 [8]. The tumor-promoting properties of the oil were associated to a specific class of phorbol diesters, exemplified by phorbol myristate acetate (PMA, TPA, 1b), having a long-chain and a short-chain acyl residue on the vicinal hydroxy groups on ring C (Type-A esters). The

• group. Partition between methanol and hexane afforded a crude mixture of phorbol diesters, that was next tritylated. After deacylation by basic treatment and chromatography, 20-tritylphorbol (1c) was obtained, as a hydrate, in sufficient purity to be used as starting material for the esterification [18

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• .13.48 Abstract This comprehensive review describes methods for the preparation of 1-indanones published in original and patent literature from 1926 to 2017. More than 100 synthetic methods utilizing carboxylic acids, esters, diesters, acid chlorides, ketones, alkynes, alcohols etc. as starting materials

• diesters: In 1951, Gilmore has demonstrated that use of esters, rather than free arylpropionic acids in phosphoric acid, in the presence of phosphorus pentoxide also led to 1-indanones in equally good or even better yields [32]. Transition metal complexes have been used by Negishi et al. as catalysts in

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• /b to diesters 26a/b/c–29a/b/c (n.d.: not determined). Reductive cleavage of 30a–c to 8-phenylmenthol (3) and 31a–c. 13C NMR data of compounds 23, 24 and 25. Facial selectivities for 26–29. Comparison of the diastereoselectivity in hetero- and homo-coupling reactions. Supporting Information

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• ], or malonate diesters via Claisen condensations followed by hydrolysis and decarboxylation. The greenest routes appear in the [4 + 2] strategy. The three-step route beginning with photochemical ring opening of cyclobutenone to give vinylketene, followed by Diels–Alder addition to ethylene leading to

Synthesis of medronic acid monoesters and their purification by high-performance countercurrent chromatography or by hydroxyapatite

• Elina Puljula,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2016, 12, 2145–2149, doi:10.3762/bjoc.12.204

• monoesters via dealkylation of medronic acid mixed tetraesters [22]. The synthesis of triesters [23] and symmetrical diesters [24] from medronic acid tetraesters has been achieved previously by using tertiary and secondary amines, for example. Unfortunately the same strategy cannot be applied to the

Solvent-free synthesis of novel para-menthane-3,8-diol ester derivatives from citronellal using a polymer-supported scandium triflate catalyst

• Lubabalo Mafu,
• Ben Zeelie and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 2046–2054, doi:10.3762/bjoc.12.193

• developed, where both hydroxy groups of para-menthane-3,8-diol could be simultaneous acylated under mild reaction conditions to form the corresponding diesters in good yields. The advantages of this method include a simple procedure from natural resources, using solvent-free reaction conditions. Keywords

• : acylation; diesters; para-menthane-3,8-diol; PS-Sc(OTf)3; Introduction Although South Africa has a substantial petrochemical industry, the fine chemical industry is very small and most chemicals are imported. As such there is significant interest in the use of natural resources for the manufacture of added

• presentation of PMD 3 conversion to the desired product at various temperatures. It can be seen on the graph in Figure 1 that the PMD 3 conversion to diesters has its optimum at lower temperatures. When the reaction is operated at 70 °C and above, dehydration of the substrate starts to occur, leading to

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Nucleic acids through condensation of nucleosides and phosphorous acid in the presence of sulfur

• Tuomas Lönnberg

Beilstein J. Org. Chem. 2016, 12, 670–673, doi:10.3762/bjoc.12.67

• phosphorous acid are hydrolytically stable compounds that are readily formed upon concentration of aqueous solutions of alcohols and phosphite salts [12]. The monoesters may react further to H-phosphonate diesters but this is an equilibrium process that under aqueous conditions favors the starting materials

• [13]. Oxidation of the H-phosphonate diester products, however, converts them to the stable phosphodiester counterparts. It is interesting to note that this reaction is faster for H-phosphonate diesters than for the respective monoesters or phosphorous acid itself [12], providing the driving force for

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• of dicarboxylic acid derivatives. Accordingly, vinyl diesters (1) and trifluoroethyl diesters (2) have been synthesized following standard procedures [16]. Moreover, succinic (3) and glutaric anhydride (4) could be used as acylating agents in controlled biocatalyzed reactions (Scheme 1) [17][18]. b

• diesters More recently, symmetric diesters have been synthetized exploiting both the activated extremities of divinyl carboxylates. C6-dicarboxylic acid diesters derivatives of the thiazoline of N-acetylglucosamine (NAG-thiazoline, 10a,b, Figure 2) were prepared and their inhibitor activities towards

• conditions for enzyme catalysis afforded nice polymers. The obtained polymers could be cross-linked by UV light in the presence of the solid photoinitiator Iracure 270 to form hard films [69]. Several poly(amine-co-ester)s were synthesized directly from dicarboxylic acid diesters and N-alkyl- or N

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• substituted selectively under milder Grignard conditions to form a single P–C bond, leaving the other ester groups intact [15][16]. Cyclic phosphorus diesters are much more reactive towards nucleophilic reagents than their acyclic analogs. Specifically, 5-membered cyclic esters of phosphonic and phosphoric

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• intramolecular cyclization of a chiral alkenylated pyrrolidinone, followed by hydroxylation [32], or by the intramolecular ring closure of chiral pyrrolidine diesters followed by ester and oxo group reduction [33], while the syntheses of (+)-epitashiromine starts from a chiral morpholine derivative, with nitrone

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• unsaturated diester followed by a sequential aldol addition and lactonization reaction [13]. To address aforementioned challenges, we have recently reported the first example of a copper-catalyzed reductive aldolization–lactonization cascade reaction of α,β-unsaturated diesters with ketones [14] and imines

• -hydroxy ester after the work-up. After lactonization, the derived methoxide reacted with a silane in a reasonable rate to recover the CuH catalyst. This is in agreement to our previously described copper-catalyzed reductive aldolization–lactonization cascade reaction of α,β-unsaturated diesters with

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

• foam, which was assumed to be the color of the desired products due to its similarity to 7 and 9. However, the presence of unreacted 5′-O-DMTr-thymidine, the starting acyls 7 and 9, and downfield 31P NMR peaks that are characteristic of diesters necessitated chromatographic separation. The isolation of

• orange color of the trityl cation was not seen. The diesters were less robust than the precursor monoester amidites. For instance, rapid chromatographic separation of the products from the ammonium salts formed during the synthesis was required to prevent further decomposition. The best procedure was

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

• to develop oligonucleotide-based drug candidates or biomedical chemical probes [5][6]. Native nucleic acids are connected by phosphate diesters as linking units, thus leading to a polyanionic backbone structure. Implications of this characteristic feature of nucleic acid architecture have been

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• in moderate to good yields. Lower yields were attributed to steric hindrance of the second and third esterifications, as well as the presence of mono- and diesters making the purification more difficult. 4-Pentynoic acid was used rather than 3-butynoic acid due to the relative price and availability

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• the diester 3 after the initial SNAr step was not necessary and decarboxylation of crude diester 3 gave 4a very efficiently. Consequently, in all analogous experiments (Table 1), crude product diesters of type 3 were isolated and used without further purification, allowing the ready synthesis of a

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• active methylidene compounds such as diesters, dinitriles of malonic acid or pentane-2,4-dione are excellent three-carbon synthons. They act as trifunctional electrophiles for the syntheses of tautomeric pyrazoles when reacted with hydrazine thereby obtaining 3,4-disubstituted pyrazoles, namely 3-amino