Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• GGPP cyclization to form the bicyclic cation 46, followed by a second cyclization and a 1,5-hydride shift to yield 47. This unusual hydride migration was experimentally supported by location of Hc at C-15 of 52. A 1,3-hydride shift generates the allylic cation 48, which can undergo another 1,5-hydride

• labeled product indicated a migration of the C-12 deuterium atoms to C-19 and to C-2, thus proving evidence for the proposed hydride migrations from 54 to 55 and from 57 to 58. The application of isotopes in mechanistic investigations is by far not limited to following atoms through the biosynthetic

• subsequent 1,2-hydride migration to 63 followed by ring closure gives 64, which is deprotonated to give pentalenene (65). Quantum chemical calculations led to the suggestion of the protoilludyl cation 66 as central intermediate between 61 and 64 (pathway B), which is directly formed from 61 [72

Total synthesis of panicein A₂

• Lili Yeung,
• Lisa I. Pilkington,
• Melissa M. Cadelis,
• Brent R. Copp and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215

• isolated from Reniera fulva and R. mucosa [2][3]. It has been postulated that the biosynthesis of paniceins centres around the cyclisation of a farnesyl precursor 6 [4] to an abscisane derivative 7 followed by a 1,2-methyl migration and subsequent oxidation to give panicein A (1) [1][3]. Subsequent

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• phosphine could interact with the electron-deficient olefin leading to catalyst decomposition [31]. As observed by us and other groups in cross metathesis involving different substrates, double bond migration side-reactions took place during this transformation. This side reaction could be circumvented

• using benzoquinone [32] as an additive to decrease the extent of double-bond migration. As depicted in Table 1 (entries 1–4), 10 mol % of benzoquinone were necessary to ensure a limited amount (<10%) of side products resulting from double-bond migration. However, addition of benzoquinone resulted in

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• was contaminated with further isomeric material. Careful analysis of the product mixtures led to the realisation that silyl migration from the primary to the secondary hydroxy group was occurring in the reaction, leading to the C20-linked ester isomer in addition to the desired C19 ester 11g. In

• -unsaturated ester 5a was formed as a mixture of diastereomers (Scheme 3), as expected, but was again contaminated with the regioisomer resulting from silyl migration (2:1 ratio 5a:isomeric C20 ester). Employing the PMB-protected C19 alcohols 7b [43][44][45] and 7c [43][44][45][49] led to the desired products

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

• respective two parent compounds. This is the so-called ‘dual drug’ strategy [37][38][39][40][41]. For instance [40][41], an increased capacity of inhibiting endothelial cell differentiation and migration (key steps of the angiogenic process) was observed as well as a marked ability to inhibit the

Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• amide in the presence of acid was discovered in 1886. This rearrangement involves the migration of a group anti to the leaving group on the nitrogen atom. The BR has widely been used in synthetic organic chemistry, for example, a large-scale production of Nylon-6 is based on the synthesis of ε

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

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• unsatisfactory, even when prolonging the reaction time to 36 h or raising the temperature to 100 °C. By carefully investigating the two routes in Scheme 3, we assumed that an appropriate base is in favor of the [1,5]H σ migration in route 2, as well as lowering the acidity of Eu(fod)3 to prevent 12b from

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• -aryl migration step. This was mediated by a hypervalent iodine reagent, PhI(OAc)2 (13), conducted in trimethyl orthoformate (14, TMOF) and methanol (Scheme 2). The direct saponification of the resulting rearranged methyl ester with an excess of base thus completed the telescoped flow synthesis of

• (Friedel–Crafts acylation, 1,2-aryl migration and saponification) this report focuses on improved output by intensifying the overall sequence (Scheme 3). As such an in-line extraction is performed after the Friedel–Crafts acylation step, followed by dissolving intermediate 18 in trimethyl orthoformate and

• DMF. This stream is then combined with a stream of ICl (21) to affect the 1,2-aryl migration in a heated flow reactor (1 min, 90 °C) followed by treatment of the stream with NaOH, 2-mercaptoethanol, MeOH and water in order to hydrolyse the intermediate methyl ester and quench residual ICl. After

DBU-promoted carboxylative cyclization of o-hydroxy- and o-acetamidoacetophenone

• Wen-Zhen Zhang,
• Si Liu and
• Xiao-Bing Lu

Beilstein J. Org. Chem. 2015, 11, 906–912, doi:10.3762/bjoc.11.102

• -diazabicycloundec-7-ene (DBU) is reported. This reaction provides convenient access to the biologically important compounds 4-hydroxy-2H-chromen-2-one and 4-hydroxy-2(1H)-quinolinone in moderate to good yields using carbon dioxide as the carboxylation reagent. An acyl migration from nitrogen to carbon is observed

• in the reaction of o-acetamidoacetophenone. Keywords: acyl migration; carbon dioxide; carboxylation; cyclization; condensation; Introduction 4-Hydroxy-2H-chromen-2-ones and 4-hydroxy-2(1H)-quinolinones are key structural subunits found in many natural products [1], commercial drugs [2][3] and

• cyclization of o-hydroxy- and o-acetamidoacetophenones with carbon dioxide to give 4-hydroxy-2H-chromen-2-ones and 4-hydroxy-2(1H)-quinolinones, respectively, in moderate to good yields under mild reaction conditions. An acyl migration from the nitrogen to carbon is observed in the reaction of o

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• receptors and result in optimal cell survival and migration signals. Growth factor-mediated activation of the receptors leads to clustering of integrins and activation of integrin signaling [8][17]. In a word, the crosstalk between integrins and growth factor receptors is bidirectional that integrins may

• . They are able to stimulate or inhibit cell proliferation, migration, differentiation, or even gene expression [46][47]. The very same growth factors might trigger different functions in different cell types, because of their pleiotropic characters [48]. The same factors can even act in opposing manner

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• [М]+) (Scheme 5). It can be assumed that ethyl cyanoacetate (12), formed as a result of ethoxymethylidene group migration to 5-AT, reacts with ester 1f to give intermediate diester 14 (Scheme 5). The latter is cyclised with 5-AT into pyridine 11 via intermediates H and I. We carried out the three

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• through inhibiting of tumor-cell proliferation, migration and induction of apoptosis. In addition, it is a dual inhibitor of the phosphorylation of VEGF and PDGF receptors, thus interrupting the angiogenetic processes required for tumor growth [30]. Recently, it was reported that its anti-angiogenesis

• neovascularization in vivo [39]. It was also shown that resveratrol directly inhibited bovine aorta endothelial cell proliferation, migration and tube formation in vitro [40]. Resveratrol has also been found to effectively interrupt VEGF-mediated tyrosine phosphorylation of vascular endothelial (VE)-cadherin and its

• the ability to prevent apoptosis, it also stimulates angiogenesis, mitogenesis, cell migration, as well as modulates cell adhesion. The presence of the 3-galloyl moiety in catechins led to higher biological activity [63][64][65], but an increasing number of aromatic hydroxy groups result in low

Synthesis of modified cyclic and acyclic dextrins and comparison of their complexation ability

• Kata Tuza,
• László Jicsinszky,
• Tamás Sohajda,
• István Puskás and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 2836–2843, doi:10.3762/bjoc.10.301

• ). Conclusions regarding the interaction affinities can be drawn based on Figure 2 and the apparent binding constants. For exploring phenomena in Figure 2 it should be noted that the closer a certain host can mobilize the analyte to the range of the electroosmotic flow (EOF, the migration range of neutral

• the case of chlorpheniramine (positively charged at this pH) prolongation of the migration time suggests the stronger interaction, while for the other guests (negatively charged at this pH) the contrary. As a demonstration of the results, the association constants calculated from the electrophoretic

Microsolvation and sp²-stereoinversion of monomeric α-(2,6-di-tert-butylphenyl)vinyllithium as measured by NMR

• Rudolf Knorr,
• Monika Knittl and
• Eva C. Rossmann

Beilstein J. Org. Chem. 2014, 10, 2521–2530, doi:10.3762/bjoc.10.263

• with the transient immobilization of one additional THF ligand, followed by stereoinversion of the quasi-sp2-hybridized carbanionic center in cooperation with a “conducted tour” migration of Li+(THF)4 along the α-aryl group within the solvent-separated ion pair. Keywords: 13C,6Li NMR coupling; ion

• the required migration shown in 13 during stereoinversion of the carbanion, as had been postulated [11] for 1. This proposal is now supported in Table 2 through the similar pseudoactivation parameters of 4&3THF (entry 3, Table 2), 2&3THF (entry 2, Table 2), and 1a&3THF (entry 1, Table 2). Although

• migration across the β-unsubstituted H2C= region in 13 might be sterically much more comfortable than across the bulky β,β-di-tert-alkyl substituents in the transition states deriving from 1 or 2, this opportunity is apparently disdained in 13: The stereoinversion is not facilitated for 4, since the ΔGψ

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• carbon skeleton to occur, this radical anion needs to react via the radical centered at its carbon atom. Grinberg et al. claim that metal or ammonium cations can cause a reversible migration of the negative charge between the carbon and oxygen atoms, allowing the CO2•− radical anion to react with its C

• -centered radical [42]. When this CO2•− radical anion abstracts a proton from the solvent, proton migration from oxygen to carbon results in formation of a strong covalent CH bond, yielding a formyloxy radical, which is further reduced to a formate anion (Table 1, entry 3). In general terms, one can

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• 5a–c. In the case of allylic azide 5a we observed an acetate migration which resulted in a complex mixture of products bearing a free hydroxy moiety (mixture of free C5-OH/C6-OH/C7-OH = 2/1/1; Scheme 1). We reasoned that this migration was limited to the inherent syn relationship between C5-OH and C6

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• does not occur in aqueous acetonitrile although diethyl phosphate is released. Other substitution patterns on the naphthyl or quinolin-5-yl core, such as the 2,6-naphthyl 10 or 8-benzyloxyquinolin-5-yl 24 platforms, also do not rearrange by aryl migration upon photolysis and, therefore, do not proceed

• application in biochemistry and chemistry [15]. We now report new pHP analogs with a fused aromatic or heteroaromatic extension of pHP. Our intent was to impose the pHP motif on the naphthyl and indolin-5-yl platforms (maintaining the critical substituent pattern) in order to foster aryl ketone migration by a

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• (Dha) derivatives under Lewis acid-mediated conditions has been investigated. The formation of 2-substituted tryptophans is proposed to occur through a selective alkylative dearomatization–cyclization followed by C3- to C2-alkyl migration and rearomatization. Keywords: Dehydroalanine; Friedel–Crafts

• alkylation; indoles; migration; tryptophans; Introduction Facile access to tryptophan and unnatural tryptophan derivatives is of general interest because tryptophans are found in many naturally occurring compounds and are an important component of biologically active compounds [1][2][3][4][5][6][7

• indole migration and rearomatization (Scheme 1, path b). Therefore, the aim of this study was to exploit the C3 Friedel–Crafts (FC) alkylation/C3- to C2 alkyl migration sequence for the synthesis of 2-substituted tryptophans [45][46][47][48][49][50]. The known methods for the synthesis of 2-substituted

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

• undergo palladium-catalyzed addition of nucleophiles to give γ-substituted vinylphosphonates 2 in high yield (Scheme 1). The nucleophile adds exclusively to the 3-position, with migration of the double bond into “conjugation” with phosphoryl group. As expected, the reactions generally proceed with

Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

• Patrick Rabe,
• Tim A. Klapschinski,
• Nelson L. Brock,
• Christian A. Citron,
• Paul D’Alvise,
• Lone Gram and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2014, 10, 1796–1801, doi:10.3762/bjoc.10.188

• . Cyclohexenone 6 was first converted with NaHMDS and TMSCl into the corresponding silylenol ether that upon oxidation with m-CPBA under migration of the TMS group yielded the protected hydroxy ketone 7. Aldol reaction with tert-butyl acetate to 8a and deprotection with TBAF gave 9a in 24% yield over four steps

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• the proton transfer step from HCN to OH−. However, 9 is less stable than 4 by 1.8 kcal/mol, indicating that the OH− prefers to capture a proton from HCN rather than from the NH3+ group. As shown in Figure 2, the rate-determining step of this reaction stage is the proton migration from the NH3+ group

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• diseases and cancer [4][5]. The role of one member of this family in particular, namely galectin-3 (Gal-3), has been intensively investigated lately and it was shown that it is deeply involved in cancer metastasis and migration. Based on these findings and with the aim to inhibit its activity and to target

Influence of perylenediimide–pyrene supramolecular interactions on the stability of DNA-based hybrids: Importance of electrostatic complementarity

• Christian B. Winiger,
• Simon M. Langenegger,
• Oleg Khorev and
• Robert Häner

Beilstein J. Org. Chem. 2014, 10, 1589–1595, doi:10.3762/bjoc.10.164

• was explained by an alternating interdigitation interaction of the pyrene with the PDI building blocks [60]. Gel migration experiments The electrophoretic mobility of relatively small (<1000 kbp), linear DNA strands is inversely proportional to their molecular weight [61]. It serves as a reliable

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• (L5) substituents. The different tendencies of Pd/L1 and Pd/L4 catalyst systems to promote isomerization of product 3 into 4 can be rationalized as follows. As discussed above (Scheme 2), the isomerization process involves reversible hydropalladation of the double bond of product 3. The migration of

• imparted by chiral ligands L4 (originally published in [64]). Mechanism of migration of C=C double bond leading to isomerization of product 3 into product 4. For discussion on isomerization 3→4 imparted by Pd/L1 complex (originally published in [64]). For discussion on isomerization 3→4 imparted by Pd/L4