Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• ’-oxoaverantin (101) into averufin (102) by intramolecular acetal formation [87]. To date, it is not clear, how exactly the OAVN cyclase participates in this process [88]. Interestingly, the OAVN cyclase operates cofactor-free, although it contains a NAD(P)+-binding Rossman fold. Furthermore, this enzyme is also

Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

• Erika Bálint,
• Ádám Tajti,
• Anna Dzielak,
• Gerhard Hägele and
• György Keglevich

Beilstein J. Org. Chem. 2016, 12, 1493–1502, doi:10.3762/bjoc.12.146

• predominance over the phosphite in the reaction, the pathway A is more likely, but if the phosphite is used in excess, the pathway B comes to the fore. There are other possibilities to synthesize (aminomethylene)bisphosphonates, such as by the reaction of dimethylformamide diethyl acetal with diethyl phosphite

• )bisphosphonates, but they are much less studied. Only a few publications were found, which focus on their synthesis [33][39][40][41][42], however, a three-component condensation has not been described. They can also be prepared starting from dimethylformamide dimethyl acetal, as in the synthesis of

Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

• Bernardas Morkunas,
• Balint Gal,
• Warren R. J. D. Galloway,
• James T. Hodgkinson,
• Brett M. Ibbeson,
• Yaw Sing Tan,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2016, 12, 1428–1433, doi:10.3762/bjoc.12.137

• route towards these derivatives involves coupling of 2 with aromatic amines to generate the corresponding amides, followed by acetal group removal under acidic conditions (Scheme 1) [9]. However, when the product of the reaction of 2 with 3 was treated with TFA, compound 4 was generated (Scheme 1). The

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• excellent yields. In the case of the reaction with o-bromobenzyl azide, the carbon–bromine bond of 3b remained intact, and other byproducts were not observed. Azides containing a linear alkyl group, acetal moiety, and a heteroaromatic ring such as pyridine gave the corresponding triazoles 3i–k in moderate

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• under the standard reaction conditions. The tosyl and 2,4,6-triisopropylbenzenesulfonyl groups on nitrogen can be removed after protection of the ketone as the cyclic acetal by using sodium naphthalide in THF (Scheme 6). After protection, the diphenylphosphoramidate group can also be removed with

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• notable that the intramolecular C–H bond insertion to form the bridged polycycle was significantly faster than an intermolecular insertion into the MOM acetal methylene, which would be electronically activated by the two flanking oxygen substituents. Later, Magnus showed that a conformationally flexible

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• -methoxybenzaldehyde acetal protecting group in 9 is believed to tie back the alcohols and prevent them from coordinating and deactivating the ruthenium catalyst. When testing the scope of the metathesis reaction with 9, a variety of partners were chosen, including not only acrylic acid (10a), but also 2-vinylpyridine

• 14, which was directly coupled to the carboxylic acid to yield 15. Finally, the desired compound 16 was obtained after acid deprotection of the p-methoxybenzaldehyde acetal in a 90% aqueous acetic acid solution (84% yield). Biological studies The antimicrobial activity of 16 was investigated. No

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• forming the appropriate aluminoxy acetal, which is expected to be stable enough at temperatures as low as −78 °C. This is partly corroborated by the decomposition of the aluminoxy acetal to the over reduced alcohol when 1.4 equiv of DIBAL-H were used (Table 1, entries 1, 3 and 5) [24]. The presence of an

• aluminoxy acetal is also supported when THF is used, although the yields are low, probably due to the destabilization of the aluminoxy acetal (Table 1, entry 4) [25]. Once established the reaction conditions, we next studied the scope and limitations of the one-pot protocol using a small subset of assorted

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• ] of 14 followed by azidolysis [41] furnished 15. 2-Azido-3,4-epoxide 18 was prepared from readily available [42] 2,3-isopropylidene-D-mannosan (16) in five steps (Scheme 2). Tosylation of 16 [43], followed by hydrolysis of the benzylidene acetal [44] and oxirane ring closure [45] at C-4 delivered 1,6

• acetal with acetic anhydride gave a mixture containing 1,2-oxazoline 41 as the main product (Scheme 5). The structure of oxazoline 41 was confirmed by single crystal X-ray diffraction analysis which also confirmed the retention of configuration during the preceding fluorine introduction. To prevent

• to furnish acetylated 3-fluoro-GalNAc 6 isolated as a separable mixture of anomers. The D-galacto configuration of 6 is manifested by the lower 3JH3,H4 coupling value (3.4 Hz, α-anomer) in comparison with that of its C-4 epimer 5 (8.6 Hz, α-anomer). Acetolysis of the internal acetal in 26 proceeded

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• aromatic macrocycle [25]. Interestingly, as these hosts are tetra-acetals we initially tried removing the template under acidic conditions. However, even reflux in 1:1 EtOH/H2SO4 for a week failed to affect the starting material. Evidently, under reversible conditions, a broken acetal can easily reform

• before the other three are themselves cleaved. An irreversible acetal cleavage mechanism is therefore key to success. Meanwhile, because our chiral canyons project required some new, tripodal zinc-binding ligands for templating a collagen helix, the whole endeavor had itself become very syntheses

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• oxymethine groups, the hemi-acetal and one of the CH2O (δ 3.65, 3.83/63.0) groups. Furthermore, the quaternary carbons included an α,β-unsaturated carbonyl (δ 165.5), an olefinic carbon (δ 137.5) and two sp3 carbons (δ 47.7 and 53.8). Fifteen carbon shifts remained after the sugar deduction suggesting the

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• , obtained via Au-catalyzed Meyer–Schuster rearrangement. Assembly of 5-oxygenated bisindolylpentenones. DMB: 3,4-dimethoxybenzyl, DMFDMA: N,N-dimethylformaldehyde dimethyl acetal. Benzylic oxidation as side reaction of DMB removal. Hydroxyalkylation of N-protected indoles with β-cyclocitral and SnCl4

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• rate-determining one and that the [1,9]-H shift is the one with the lowest energy barrier. Keywords: acetal; benzindenes; DFT calculations; fulvene; hydrogen shift; Introduction Fulvenes (also known as pentafulvenes), [1][2][3][4] a unique class of trienes, have intrigued chemists for decades due to

• wondered whether acetalic functions could be employed as internal H donors in intramolecular hydride-like shifts, analogous to that highlighted in Scheme 1, toward fulvene frameworks. With this goal in mind we designed the unknown acetal-fulvenes 3 (Scheme 2) as potential candidates for assaying the [1,4

• Experimental study The starting acetal-fulvenes 3 were prepared by the condensation of substituted 2-(1,3-dioxolan-2-yl)benzaldehydes 4 with cyclopentadiene following a well-established synthetic methodology [33]. With the aim of promoting the desired hydride transfer by thermal activation, we first heated the

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• alkynylations in good yields and ee’s. In 2011, we reported the first example of enantioselective alkynylation of a cyclic oxocarbenium ion intermediate (Scheme 15) [55]. Isochroman oxocarbenium ion 41 was formed in situ via Lewis acid-mediated ionization of a racemic acetal precursor. By using a Cu(MeCN)4PF6

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• benzylic bromination followed by elongation of the C3 unit [22]. To this end, the ester group at the C1 position of 15 was reduced by lithium borohydride, and the resultant 1,3-diol protected to give acetal 16 [16]. After various experiments, selective bromination of the methyl group on the aromatic ring

• % yield (dr > 10:1) via the method established in Scheme 3. After derivatization to acetal 22 in 2 steps, we then turned our attention to the introduction of the C4 ester substituents. Amongst various different conditions investigated – including Pd-catalyzed coupling reactions – a halogen-lithium

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• example, disulfide [10], acetal [11], imine [12] and boronates [13][14][15][16], to allow the generation of new covalent structures under thermodynamic control. Complete esterification is observed for boronate esters bearing ortho-amines [17]. The conceptual advantage compared to traditional irreversible

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• , J = 12.0, 5.3 Hz, 4H, 2-Ha), 2.59 (dd, J = 11.7, 2.9 Hz, 4H, 6-Ha), 2.47–2.41 (m, 8H, 2-Hb + 6-Hb), 2.36 (t, J = 6.6 Hz, 8H, 1’-H), 2.11–2.03 (m, 8H, 2’-H), 1.49 (s, 12H, Me), 1.35 (s, 12H, Me) ppm; 13C NMR (50 MHz, CDCl3) δ 145.1 (s, 4C, C-triazole), 123.3 (d, 4C, C-triazole), 109,0 (s, 4C, acetal

• + OCH2CNH), 2.60–2.43 (m, 27H, 2-H + 1’-Ha), 2.82–2.51 (m, 27H, 6-H + 1’-Hb), 1.99–1.95 (m, 18H, 2’-H), 1.43 (s, 27H, Me), 1.35 (s, 27H, Me) ppm; 13C NMR (100 MHz, CDCl3) δ 166.5 (s, 3C, C=O), 144.4 (s, 9C, C-triazole), 135.6 (s, 3C, Ar), 128.6 (d, 3C, Ar), 123.7 (d, 9C, C-triazole), 109,0 (s, 9C, acetal

• , 1H, 2-Ha), 2.70–2.64 (m, 1H, 6-Ha), 2.51–2.43 (m, 1H, 2-Hb), 2.40–2.30 (m, 2H, 1’-H), 2.11–2.03 (m, 3H, 6-Hb + 2’-H), 1.48 (s, 3H, Me), 1.33 (s, 3H, Me) ppm; 13C NMR (100 MHz, CD3OD) δ 146.8 (s, C-triazole), 122.6 (d, C-triazole), 108.7 (s, acetal), 78.7 (d, C-4), 73.1 (d, C-3), 69.0 (d, C-5), 56.0

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• subfamilies: the xenicins (containing an 11-oxabicyclo[7.4.0]tridecane ring system with an acetal functionality) [2], the xeniolides (containing an 11-oxabicyclo[7.4.0]tridecane ring system with a lactone functionality) [3] and the xeniaphyllanes (with a bicyclo[7.2.0]undecane ring system) [4]. Later, an

• . Addition of lithium acetylide 41 to the keto group led to acetal 42. Hydrogenation of the triple bond under basic conditions resulted in cleavage of the acetal and ring closure to the corresponding lactol which was oxidized with chromic acid to furnish γ-lactone 43. An ensuing Dieckmann condensation [32

• -catalyzed and base-mediated cyclization of carbonate 71 [45]. Reductive cleavage of the sulfone using aluminium amalgam afforded a ketone, which was converted to an exocyclic double bond by treatment with Tebbe’s reagent [42]. In order to convert the methoxy acetal to the corresponding lactone, without

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• employed in this work, with increased surface area-to-volume ratio, allows effective heat dissipation under ambient conditions. Continuous reactor A nylon/PTFE tubular reactor was constructed that incorporates static mixers for enhanced mixing of the biphasic reaction solution, made of the acetal

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• -Iodoindole (4) was prepared from 1-iodo-4-methyl-3-nitrobenzene (3, accessible from the corresponding nitroaniline via Sandmeyer reaction) via the Batcho–Leimgruber protocol employing dimethylformamide dimethyl acetal (DMFDMA) and TiCl3 in one step. It should be noted that, after initial column filtration of

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• synthesis [65]. This preparation started with a Knoevenagel condensation of 2-fluoroacetophenone with malononitrile. The product of the condensation reacted with an excess of N,N-dimethylformamide dimethyl acetal to afford an enamine. This latter was treated with hydrochloric acid in acetic acid gave 4-aryl

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• , with the structure and stereochemistry confirmed by X-ray crystallography. The two others were obtained during a total synthesis of erythronolide Al [55][56], as a result of deprotection of the 3,5-benzylidene acetal of erythronolide A (with or without a triethylsilyl protecting group on 6-O). However

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

A hybrid electron donor comprising cyclopentadithiophene and dithiafulvenyl for dye-sensitized solar cells

• Gleb Sorohhov,
• Chenyi Yi,
• Michael Grätzel,
• Silvio Decurtins and
• Shi-Xia Liu

Beilstein J. Org. Chem. 2015, 11, 1052–1059, doi:10.3762/bjoc.11.118

• , the synthesis of the key intermediate 7 involves the protection of one aldehyde group as an acetal using pinacol prior to HWE reaction of 5 with 4,5-bis(hexylthio)-1,3-dithiole-2-thione, followed by deprotection under acidic conditions. Aldehyde 5 was readily obtained by palladium-catalyzed Suzuki

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60