Engineering Pichia pastoris for improved NADH regeneration: A novel chassis strain for whole-cell catalysis

• Martina Geier,
• Christoph Brandner,
• Gernot A. Strohmeier,
• Mélanie Hall,
• Franz S. Hartner and
• Anton Glieder

Beilstein J. Org. Chem. 2015, 11, 1741–1748, doi:10.3762/bjoc.11.190

• single knock-out strains, respectively. The behavior of the das knock-out strains in heterologous protein production was tested by expressing green fluorescent protein (GFP) under the control of the AOX1 promoter (PAOX1), which is the most prominent, methanol inducible promoter for P. pastoris. A

• Vogl (TU Graz, Austria) for providing the plasmid harboring the coding sequence of GFP under the control of the AOX1 promoter. The research leading to these results has received funding from the Innovative Medicines Initiative Joint Undertaking project CHEM21 under grant agreement n°115360, resources

The facile construction of the phthalazin-1(2H)-one scaffold via copper-mediated C–H(sp²)/C–H(sp) coupling under mild conditions

• Wei Zhu,
• Bao Wang,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 1624–1631, doi:10.3762/bjoc.11.177

• the impact of various inorganic bases and K2CO3 proved to be the most efficient promoter (Table 1, entries 1–7). The subsequent evaluation of copper salts revealed that Cu(OAc)2 gave the best yield (Table 1, entries 8–11). The effect of different solvents on the transformation was also investigated

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• -hydroxy derivatives of D-glucose and L-rhamnose [49]. Glycosylation of diosgenin with twelve different derivatives of D-glucosamine (2a–d, 3a–d, and 5a–d), was examined using “normal” and “reverse” procedures [50] (Table 1). In the “normal” procedure, the promoter (silver triflate or trimethylsilyl

• triflate) was added to the solution of diosgenin and the respective glycosyl donor. In the “reverse” procedure, the respective glycosyl donor was added to the solution of diosgenin and the promoter. Diosgenin glycosylations were carried out in dichloromethane or/and in a mixture of dichloromethane and

Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

• Marina Bantzi,
• Stephan Rigol and
• Athanassios Giannis

Beilstein J. Org. Chem. 2015, 11, 604–607, doi:10.3762/bjoc.11.67

• ][23] was linked with glycosyl acceptor 2 [24][25] using TMSOTf as promoter to obtain disaccharide 4 in 90% yield. Likewise, reaction of glycosyl donor 1 with monosaccharide 3 [26] and subsequent O-TBS group cleavage with Olah's reagent [27], afforded disaccharide 5 in 86% yield. Thence, both

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

• Radhey M. Singh,
• Kishor Chandra Bharadwaj and
• Dharmendra Kumar Tiwari

Beilstein J. Org. Chem. 2014, 10, 2975–2980, doi:10.3762/bjoc.10.315

• Abstract The Morita–Baylis–Hillman reaction of acrylamide, as an activated alkene, has seen little development due to its low reactivity. We have developed the reaction using isatin derivatives with acrylamide, DABCO as a promoter and phenol as an additive in acetonitrile. The corresponding aza version

A comparative study of the interactions of cationic hetarenes with quadruplex-DNA forming oligonucleotide sequences of the insulin-linked polymorphic region (ILPR)

• Darinka Dzubiel,
• Heiko Ihmels,
• Mohamed M. A. Mahmoud and
• Laura Thomas

Beilstein J. Org. Chem. 2014, 10, 2963–2974, doi:10.3762/bjoc.10.314

• that consists of repetitive DNA units with varying length and sequence [1]. The ILPR is located in the promoter region of the human insulin gene and is proposed to control the expression of the latter. It was shown that insulin-dependent diabetes mellitus (IDDM, type-I diabetes) is associated with the

• observation that insulin associates with quadruplex DNA [10]. In particular, it was assumed that the formation of quadruplex structures affects the transcriptional activity, because the position of the ILPR in the promoter region of the gene represents a stake close to the transcription process [9][11][12

Galactan synthesis in a single step via oligomerization of monosaccharides

• Marius Dräger and
• Amit Basu

Beilstein J. Org. Chem. 2014, 10, 2658–2663, doi:10.3762/bjoc.10.279

• the donor to a solution of 3 and La(ClO4)3 might reduce self-oligomerization. However, addition of 2 via a syringe pump did not significantly improve the yields, nor did it shift the product distribution to longer oligomers. The use of La(ClO4)3 as the promoter appears to be critical in this reaction

• did not result in any significant changes (Table 1, entry 7). Finally, the use of Hf(OTf)4 as a promoter [24] was completely ineffective and no glycosylation was observed (Table 1, entry 8). Carrying out the reaction in the absence of base did not have a significant effect, although it minimally

A general metal-free approach for the stereoselective synthesis of C-glycals from unactivated alkynes

• Shekaraiah Devari,
• Manjeet Kumar,
• Ramesh Deshidi,
• Masood Rizvi and
• Bhahwal Ali Shah

Beilstein J. Org. Chem. 2014, 10, 2649–2653, doi:10.3762/bjoc.10.277

• , India 10.3762/bjoc.10.277 Abstract A novel metal-free strategy for a rapid and α-selctive C-alkynylation of glycals was developed. The reaction utilizes TMSOTf as a promoter to generate in situ trimethylsilylacetylene for C-alkynylation. Thanks to this methodology, we can access C-glycosides in a

• characterized by a requirement of pre-formed trimethylsilylacetylene. Results and Discussion Initial investigations involved the use of 3,4,6-tri-O-acetyl-D-glucal (1) and phenylacetylene (2) as model substrates with TMSOTf as a promoter within DCM at −20 °C. To our delight TLC showed full consumption of the

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• fragments. The product of the autonomous assembly was then ligated behind a β-galactosidase promoter in a plasmid containing a gene conferring resistance to ampicillin. This was used to transform E. coli cells, which were found to grow in medium containing kanamycin. Plating experiments quantitated these

• µg/mL) and IPTG (1 mM). Single colonies were then used to inoculate cultures grown in the presence of ampicillin alone. Plasmids were harvested with the Zyppy™ Miniprep kit (Zymo Research) and were sent out to be sequenced with vector primers (T7 Terminator and T7 Promoter long). The sequences

• transformed by plasmids containing the self-assembled kanamycin-resistance gene placed behind a β-galactosidase promoter in the TOPO expression vector (Invitrogen), but without selection for resistance to kanamycin. (a) The cell culture was diluted in two steps by a factor of 267,000. Then, aliquots (25 µL

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• of 59% during a reaction time of 15 min when a catalytic amount of HClO4 (20 mol %) was used as GBB-3CR promoter [7] in EtOH. 1D- and 2D NMR techniques (1H,13C-HSQC, 1H,13C-HMBC, 1H,1H-COSY and 1H,1H-NOESY) confirmed the exclusive presence of a 1H-imidazo[1,2-b]pyrazole core with an endocyclic double

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• -substituted 1,2-oxazines to bicyclic ketones has been described in many examples [24]. Gratifyingly, starting from 1,2-oxazine 4 with tin(IV) chloride as Lewis acidic promoter the corresponding ketone was obtained in excellent stereoselectivity. The subsequent protection of the primary hydroxy group as TBS

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• upon adding MgBr2, even though this promoter was shown to perform well in other reactions on ketimine 1. Evidently, in this case, the effective protonation of the nitrogen would be required in order to efficiently carry out the attack of the moderately nucleophilic isonitrile. An increase of the

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• copies of the luciferase and β-galactosidase genes under the control of the HIV-1 promoter [37][38][39][40]. Drugs, ester derivatives and GNPs were incubated with HIV-1 virus (NL4-3 strain) in triplicate for 30 min at 37 °C. The virus–drug mixture was added (1:1 by volume) to 10,000 TZM-bl cells per well

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• coordination of the lithium cation to the nitrone oxygen is possible. The Lewis acid-induced rearrangements of 1,2-oxazines syn-7, syn-9 and syn-10 were achieved in moderate to good yields using TMSOTf as promoter (Scheme 4). A higher yield of 73% was achieved for the p-bromophenyl derivative 13 (isolated as a

Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1–DNA-complex formation

• Midori A. Arai,
• Kyoko Uchida,
• Samir K. Sadhu,
• Firoj Ahmed and
• Masami Ishibashi

Beilstein J. Org. Chem. 2014, 10, 134–140, doi:10.3762/bjoc.10.10

• interacts with the Shh protein [12], and JK184 induces Hh inhibition through class IV alcohol dehydrogenase [13]. GANT-61 is an inhibitor, which disturbs GLIs binding to their binding site (GACCACCCA) in the promoter region of the target genes [14]. The AAA+ ATPase motor cytoplasmic dynein has been found to

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• production of inhibitors of survivin promoter activity, a new drimane sesquiterpene lactone, SF002-96-1, was isolated from fermentations of an Aspergillus species. The compound inhibited survivin promoter activity in transiently transfected Colo 320 cells in a dose dependent manner with IC50 values of 3.42

• attractive target for new anticancer therapeutics [13]. In a search for new inhibitors of survivin expression from natural sources, we found that cultures of Aspergillus sp. strain IBWF002-96 produced a new drimane sesquiterpene lactone, SF002-96-1, with inhibitory activity on survivin promoter activity in

• secondary metabolites and the characterization of their influence on survivin expression, we employed a human survivin-promoter dependent transcriptional reporter in the transiently transfected human colorectal carcinoma cell line Colo 320. Due to the overexpression of survivin in many human cancers

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

• forming reactions of organylzirconocene nucleophiles (Scheme 21) [77]. They used AgAsF6 as the Lewis acid promoter and found that also Garner’s aldehyde reacts under these conditions with 1-hexenylzirconocene. The reaction gave a good yield of the addition products 56 and 57 (70% combined yield), but no

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• eleven, gold has also demonstrated to be an efficient promoter of intermolecular carbene transfer reactions from diazo compounds to unsaturated systems such as alkenes or alkynes, resulting in cyclopropanation processes [44][45]. The development of an enantioselective variant of this type of reactions

• promoter of the cyclopropanation between donor–acceptor diazooxindoles such as 9 and a broad range of alkenes (Scheme 6) [47]. The resulting spirocyclopropyloxindoles 10, which are obtained in excellent yields and enantioselectivities, are appealing structures from a medicinal point of view. The scope of

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• in the presence of 0.5 equiv of quinidine, the corresponding rearranged product 94 was obtained in 41% yield with 52% ee. The other P,C-chirogenic phospholene derivative 93 was produced by using 100 mol % cinchonidine as a promoter (Scheme 14). But this desymmetrization process is extremely sluggish

Preparation of optically active bicyclodihydrosiloles by a radical cascade reaction

• Koichiro Miyazaki,
• Yu Yamane,
• Ryuichiro Yo,
• Hidemitsu Uno and
• Akio Kamimura

Beilstein J. Org. Chem. 2013, 9, 1326–1332, doi:10.3762/bjoc.9.149

• methylthiyl radical also undergoes such a radical cascade reaction to stereoselectively give bicyclic dihydrothiophenes [16]. We expected that tris(trimethylsilyl)silane (Me3Si)3SiH [17], which is a well-known alternative to Bu3SnH in radical reactions [18][19][20][21][22], would be a good promoter of a

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• that inhibit gene expression mediated by this Rho/MKL1/SRF signaling pathway [8]. The lead CCG-1423 (1, Figure 1) was identified in a cell-based high-throughput screen as an inhibitor of expression of a luciferase reporter gene driven by the serum response element promoter (SRE-Luc) [9]. Analysis of

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

• Leandro Lara de Carvalho,
• Robert Alan Burrow and
• Vera Lúcia Patrocinio Pereira

Beilstein J. Org. Chem. 2013, 9, 838–845, doi:10.3762/bjoc.9.96

• nitroalkenes 5a–c as heterodienes, ethyl vinyl ether (EVE) as a dienophile, and selected electron-deficient alkenes as 1,3-dipolarophiles. The employment of different organic solutions of LiClO4 or LiCl as promoter systems provided the respective nitroso acetals with yields from 34–72% and good levels of

• addition of a Lewis acid as a promoter reaction; however, a limited number of these species have been employed in these reactions, e.g., SnCl4 or Ti(O-iPr)2Cl2 [1][2][3]. However, LiClO4 or LiCl solutions have not been used in tandem nitroalkene cycloadditions, although they are widely employed as

• system, the reactivity of 5a,b with EVE and methyl acrylate (MA) as a dipolarophile was evaluated in the absence of a promoter. In all experiments conducted, the cycloadducts were obtained in 18–70% yield with total chemo- and regioselectivity including good levels of diastereoselectivity (Table 1). The

A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-γ-aminated nitroalkenes derived from L-α-amino acids

• Vera Lúcia Patrocinio Pereira,
• André Luiz da Silva Moura,
• Daniel Pais Pires Vieira,
• Leandro Lara de Carvalho,
• Eliz Regina Bueno Torres and
• Jeronimo da Silva Costa

Beilstein J. Org. Chem. 2013, 9, 832–837, doi:10.3762/bjoc.9.95

• . On the other hand, the neat benzylamine addition, or in the presence of DBU (0.5 equiv) as promoter [84], to 2a,b was unsuccessful (Table 1, entries 14 and 15). This nonreactivity can be explained on the basis of the high tendency toward reversibility presented in conjugate additions of amines to

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• employing a PC12 (phenochromacytoma) cell line stably expressing the human SOD1 promoter flanked by green fluorescent protein (GFP) [25]. This screening strategy identified 20 compound hits, for which the activity was confirmed through secondary assays and analyzed for cytotoxicity. Compound 7687685 (8

• pyrimethamine. In contrast, these studies found that the concentrations of pyrimethamine required to reduce transcriptional activity from the SOD1 promoter by 42% caused a 68% reduction in cellular viability, thus leading to the conclusion that the reduction in SOD1 levels was due to nonspecific cytotoxicity

• stress-induced proteins showed increased expression, and activation of the Nrf2 transcription factor also increased. Compound 30 was demonstrated to induce ARE promoter activity in SH-SY5Y cells by using a luciferase reporter assay [65]. These data demonstrate that 30 confers resistance to oxidative

Short synthesis of the common trisaccharide core of kankanose and kankanoside isolated from Cistanche tubulosa

• Goutam Guchhait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 705–709, doi:10.3762/bjoc.9.80

• case, NOBF4 acts as a promoter for the activation of the glycosyl trichloroacetimidate derivative as well as the acetylation of the sugar derivative with acetic anhydride. The formation of compound 6 was confirmed by its spectral analysis [signals at δ 5.44 (s, PhCH), 4.79 (br s, H-1B), 4.37 (d, J