Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• . Indeed, these highly electrophilic cyclic vinylogous amides are known to undergo facile nucleophilic additions [21][22][23][24][25], sometimes accompanied with subsequent pericyclic rearrangements [26][27][28][29][30][31][32][33]. Not surprisingly, these versatile synthons have been successfully employed

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• Cope sigmatropic rearrangements. Normally, this reaction proceeds through a transition state with a chair conformation. However, the transformation of schkuhriolide (germacrane) into elemanschkuhriolide (elemane) may occur through a boat transition state due to the final configuration of the

• into elemanes by heating through a Cope rearrangement. In some cases, these transformations are so favorable that it has been mentioned that the observed elemanes are only artifacts produced at the extraction [5][6][7][8]. It is known that 1,5-dienes suffer Cope rearrangements at temperatures between

• mechanism could have significant contributions from other mechanisms that involve radical species [13][16][20][23][24][25][26][27]. Detailed discussions about Cope rearrangements can be found in several studies and reviews that have been published previously [20][28][29][30][31][32]. The configuration of

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• rearrangements. Many examples demonstrate that the mechanochemical approach to synthesis enhances the already described reactivity patterns, but also allows the development and discovery of novel reactions under milling conditions. The possibility to conduct mechanochemical reactions in near-quantitative yields

18-Hydroxydolabella-3,7-diene synthase – a diterpene synthase from Chitinophaga pinensis

• Jeroen S. Dickschat,
• Jan Rinkel,
• Patrick Rabe,
• Arman Beyraghdar Kashkooli and
• Harro J. Bouwmeester

Beilstein J. Org. Chem. 2017, 13, 1770–1780, doi:10.3762/bjoc.13.171

• cascade by attack of olefinic double bonds to the cationic centre, hydride shifts and Wagner–Meerwein rearrangements. The process is usually terminated by deprotonation or attack of water to yield a lipophilic terpene hydrocarbon or alcohol. Among the first investigated terpene synthases were the (+)- and

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• fibroblasts, which are extremely mycolactone-sensitive. Upon exposure to natural mycolactone A/B concentrations as low as 0.025 ng/mL (0.034 nM), L929 cells show cytoskeletal rearrangements at 12 h, cell rounding within 24 h and a loss of adhesion along with growth arrest after 48 h [32]. At this point, the

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• example for such a “chiral pool” starting material is camphor. Both its substituents and its bicyclic skeleton can easily be modified and adapted to the purpose at hand, e.g., natural product synthesis [5]. The Wagner–Meerwein and Nametkin-type rearrangements are the most common reaction patterns [6] and

• (Scheme 1) [20]. A hydroxy group neighbouring an alkynyl substituent, under treatment with acids, normally leads to Rupe and Meyer–Schuster rearrangements, forming unsaturated carbonyl compounds. This was indeed observed in camphor-derived bicyclic alcohols containing a single ethinyl group [21][22

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• an aldehyde hydrate moiety associated to free AnGal, such a strategy could be conducted through reductive amination reactions. Even though reductive amination has been widely used in organic synthesis, its applicability remains challenging when dealing with carbohydrates [18][19][20]. Rearrangements

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• crystal-packing forces are large enough to change the induction state of the tetracycline repressor [26]. GPCR simulations often also show geometric rearrangements after several hundred nanoseconds, which suggests that the simulation is perhaps switching to a conformation closer to the biologically

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• mainly rely on the use of rearrangements and chain elongation reactions [17]. Rearrangement reactions such as the Lobry de Bruyn rearrangement and the Bilik rearrangement employ unprotected aldoses as substrates, usually yielding an equilibrium mixture of aldoses and ketoses [18][19]. In addition to

Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study

• Franca Castiglione,
• Fabio Ganazzoli,
• Luciana Malpezzi,
• Andrea Mele,
• Walter Panzeri and
• Giuseppina Raffaini

Beilstein J. Org. Chem. 2017, 13, 714–719, doi:10.3762/bjoc.13.70

• the inclusion is much faster in the case of molecule 2, being essentially complete within the initial 20–30 ps of the MD run, apart from some smaller and lengthier rearrangements at longer times. Such very fast process is possibly related to the larger or smaller rigidity of the central ring in the

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• of drug molecules. These changes may involve overall backbone structure rearrangements or they can be subtle where only the side chains near the ligand binding site change to accommodate the bound ligand. However, this dynamic nature of targets is frequently ignored and protein flexibility is

High performance p-type molecular electron donors for OPV applications via alkylthiophene catenation chromophore extension

• Paul B. Geraghty,
• Calvin Lee,
• Jegadesan Subbiah,
• Wallace W. H. Wong,
• James L. Banal,
• Mohammed A. Jameel,
• Trevor A. Smith and
• David J. Jones

Beilstein J. Org. Chem. 2016, 12, 2298–2314, doi:10.3762/bjoc.12.223

• transmitted spectrum during the phase change recorded at 164 °C, Figure 2, suggestive of significant structural rearrangements occurring during crystallization. The POM/heating stage apparatus was coupled to a fibre-optic based spectrometer to enable collection of variable temperature UV–vis and fluorescence

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

• unnamed rearrangement reactions of peroxides. It should be noted, that in the chemistry of peroxides two types of processes are considered under the term rearrangements. These are conventional rearrangements occurring with the retention of the molecular weight and transformations of one of the peroxide

• moieties after O–O-bond cleavage. Detailed information about the Baeyer−Villiger, Criegee, Hock, Kornblum−DeLaMare, Dakin, Elbs, Schenck, Smith, Wieland, and Story reactions is given. Unnamed rearrangements of organic peroxides and related processes are also analyzed. The rearrangements and related

• rearrangements and related processes play an important role in the chemistry of oxidation processes. Thus, the key reagent in the Sharpless epoxidation of allylic alcohols [48] and in the manufacture of propylene oxide via the Prilezhaev reaction [49][50][51] is tert-butyl hydroperoxide. In industry, phenol and

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

• annelated with a δ-lactone and a cyclopentanone or oxidation products of the latter. Aflatoxin biosynthesis has been studied since the late 1960s and has attracted attention, because the polyketide undergoes a series of oxidative rearrangements, which drastically alter the molecular scaffold. Due to the

• synthase (NorS) (Scheme 16) [83][85]. NorS is a complex of a NR-PKS PksA and a pair of yeast-like fatty acid synthases HexA/HexB, which provide an unusual hexanoyl-CoA starter unit [86]. Norsolorinic acid (100) undergoes three oxidative rearrangements towards aflatoxin B1 (94): The first rearrangement sets

Ring-whizzing in polyene-PtL₂ complexes revisited

• Oluwakemi A. Oloba-Whenu,
• Thomas A. Albright and
• Chirine Soubra-Ghaoui

Beilstein J. Org. Chem. 2016, 12, 1410–1420, doi:10.3762/bjoc.12.135

• ; density functional theory (DFT); hapototropic rearrangements; HOMO–LUMO interactions; polyene-ML2 complexes; ring-whizzing; Introduction Polyene–transition metal complexes were found to undergo fluxional rearrangements as early as 1956 with the preparation of Cp2Fe(CO)2 [1]. The migration of an MLn unit

• around the periphery of a cyclic polyene is commonly called ring-whizzing, purportedly ascribed to Rowland Pettit [2]. A more inclusive term is haptotropic rearrangement [3] wherein a metal atom changes its hapticity along the reaction path. Haptotropic rearrangements in ML3 and MCp complexes are

• of us undertook a theoretical survey of these compounds at the extended Hückel level a number of years ago [20][21]. In the present contribution we shall revisit some of these rearrangements using DFT theory, as well as, investigate some new compounds. A d10 ML2 fragment possesses a high-lying HOMO

The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• isolated from the producing organism. Deuterium labellings also allow to follow hydrogen rearrangements, but non-specific hydrogen migrations during the fragmentation process and kinetic isotope effects can make data interpretation difficult. In contrast, the introduction of 13C-labelling into a terpene

• yield C1+ that upon hydrogen rearrangements via D1+ to E1+ and inductive cleavage of water results in the conjugated cation F1+. Since the 13C-labelling experiments presented in this study cannot distinguish which of the hydrogens of 1 are rearranged or lost, alternative mechanisms may contribute to the

• +·, followed by an inductive cleavage with neutral loss of isobutyraldehyde to H2+·. This reactive intermediate can stabilise to the conjugated radical cations I2+· or J2+· by two alternative hydrogen rearrangements. PMA135 for the base peak ion m/z = 135 reveals that this fragment ion is produced from C1–C9

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• types of reactions include the alkylation of the imine nitrogen atom followed by ring annulation [6], cleavage of the sulfonimine [7][8] or camphor [9] rings, reduction of the CO or CN double bonds [10], addition of acetylide anions to form dialkynes that can undergo complex skeletal rearrangements and

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• these aspects of reaction mechanisms. Unique potential energy surface topologies associated with these rearrangements have been discovered in recent years that are not only of fundamental interest, but also provide insight into the way Nature manipulates chemical space to accomplish specific chemical

• transformations. Cautions for analyzing both experimental and theoretical data on carbocation rearrangements are included throughout. Keywords: carbocation; density functional theory; dynamics; mechanism; terpene; Review Introduction to terpene forming carbocation rearrangements Terpene natural products display

• commonly used [35][36][37][38][39][40]. In particular, the B3LYP and mPW1PW91 functionals, along with small to medium sized basis sets have seen the most use in studying carbocation rearrangements of relevance to biosynthesis [6]. Using molecular dynamics trajectories to rationalize experimental results is

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

• ketone 26 proceeded in the highest yield of all our Meyer–Schuster rearrangements. With triflated α,β-unsaturated ketone 26 in hand, we attempted reductive Heck cyclizations to the raputindole core structure. For instance, we employed Pd(dba)2 (12 mol %), QPhos (24 mol %), and NEt3 (1.20 equiv) in DMF at

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

• construction of diverse fused ring systems. Other classical pericyclic processes that may potentially occur in fulvene fragments (electrocyclic and ene reactions, sigmatropic rearrangements and shifts) have received less attention, most probably with the only exception of the Claisen rearrangement [16

Aggregation behavior of amphiphilic cyclodextrins in a nonpolar solvent: evidence of large-scale structures by atomistic molecular dynamics simulations and solution studies

• Giuseppina Raffaini,
• Fabio Ganazzoli and
• Antonino Mazzaglia

Beilstein J. Org. Chem. 2016, 12, 73–80, doi:10.3762/bjoc.12.8

• systems with a total of sixty-four molecules produced significant rearrangements with the formation of extended structures with a long-range connectivity due to intermolecular non-bonded interactions again reproducing those previously mentioned. The first of these extended structures is shown in Figure 5

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

• commonly employed method for the synthesis of cyclononenes due to the predictability of the stereochemical outcome of the product. The construction of cyclononenes can furthermore be achieved by thermal [3,3]-sigmatropic rearrangements of 1,5-dienes C. When the reaction proceeds via a chairlike transition

• , several strategies for the preparation of the characteristic nine-membered carbocyclic ring structures have been developed. The synthetic strategies are typically based on ring expansion (Grob-type fragmentation and sigmatropic rearrangements), ring closing (metathesis and transition metal-catalyzed

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

• rearrangements and cyclizations experimentally. The structure elucidation of terpenoids can be challenging because of the multicyclic carbon skeletons with several contiguous stereocenters. The assistance of 13C labels can in such cases be especially helpful, and if completely 13C-labeled carbon backbones can be

Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

• Giuseppina Raffaini,
• Antonino Mazzaglia and
• Fabio Ganazzoli

Beilstein J. Org. Chem. 2015, 11, 2459–2473, doi:10.3762/bjoc.11.267

• equilibration criteria, the MD runs were carried out for different lengths. The simulations in explicit water were often shorter than in vacuo due to the much larger computational burden of a fully hydrated system, so that much lengthier rearrangements cannot be ruled out. On the other hand, system

• allow for possible major rearrangements of the two molecules, as indeed found in the fully optimized geometries shown in Figure 6 at left. In particular, the H–H and H–P initial arrangements display an almost complete rotation and/or a noticeable tilt of one molecule with respect to the other one

• arrangements of the two aCD (or more precisely in the distance between the centers of mass of the two aCD), which can require a longer simulation time to achieve equilibrium by small local rearrangements than potential energy. Accordingly, the initial interaction geometry kinetically traps the adducts in a

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• Liebeskind and coworkers due to its modularity and control of regioselectivity and wondered if a Chan–Lam route to N-alkenylnitrones would allow us to prepare similar intermediates (Scheme 2A) [51]. Nakamura and coworkers have reported that N-allenylnitrones can be accessed through rearrangements of O