Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

• Jason Yin Hei Man and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2019, 15, 1829–1837, doi:10.3762/bjoc.15.177

• discussed above, isomers I and III will both give two sets, whereas the symmetrical isomer II will give one set of triazole and CB[6] signals. The NOESY spectrum of 5R may not provide further information due to the complexity of the spectrum (Figure S14 in Supporting Information File 1), and further

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• compounds characterized by several important features, e.g., molecular complexity and diversity at different levels, high variability and easy accessibility from relatively simple reagents. These challenges can be overcome by using multicomponent reactions (MCRs) but also other strategies can be applied in

• characterized by the complexity and diversity of the skeleton itself gained through multi-step transformations (group II) [18][19][34][35][36] or allow for generating additional diversity through post-cyclization reactions (group III) [18][35][36][37][38][39][40][41][42]. Meanwhile the complexity of the acid

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• and complexity-generating processes [2][3] have proven success in peptide ligation [4] and macrocyclization [5][6], protein glycoconjugation [7], lipidation of peptides [8] and glycosides [9], and carbohydrate modification [10]. A special class of lipidic biomolecules are the steroids, which can be

• , Wessjohann’s group exploited the MiBs strategy based on the Ugi-4CR for the assembly of topologically diverse steroidal macrocycles incorporating a variety of (seco)steroid skeletons [70][71][72]. Probably the highest level of macrocycle complexity achieved in one-pot can be found in the multicomponent

• . Thus, cholanic dicarboxylic acids 73 and 74 were macrocyclized with a paraformaldehyde-derived diimine and two different aryl diisocyanides to furnish steroidal cages 75 and 76 in good yields considering the structural complexity created in a single synthetic operation. It is worth mentioning that due

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• Information File 1). Taken together, the overall more sluggish conversion of GPP and GGPP by the TS leading to enantiomeric mixtures, the higher biosynthetic complexity of the obtained sesquiterpenes and the absence of spontaneous hydrolysis products in the incubation with FPP compared to the appearance of 14

Halogen bonding and host–guest chemistry between N-alkylammonium resorcinarene halides, diiodoperfluorobutane and neutral guests

• Fangfang Pan,
• Mohadeseh Dashti,
• Michael R. Reynolds,
• Kari Rissanen,
• John F. Trant and
• Ngong Kodiah Beyeh

Beilstein J. Org. Chem. 2019, 15, 947–954, doi:10.3762/bjoc.15.91

• high Z’-value structure. Disorder is not inherently a feature of a poor structure, disorder instead indicates the complexity of the dynamic solution state. Solving it, however, remains a challenge. N-Alkylammonium resorcinarene halides (NARXs) have been extensively studied in our groups as multidentate

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• of the starting materials in an atom-economic process [9][10][11]. A high level of molecular complexity can be generated in a single step and, by varying the structure of each component, different libraries of molecules can be easily obtained. Compared to a sequential synthesis, this strategy

• to be used directly to obtain macrocycles of this complexity and size. The synthesis of macrocycles with up to 16 new bonds being formed simultaneously has been described (Scheme 22). The strategy was based on combining steroidal dicarboxylic acids 115 and biaryl ether diisocyanide 116 [38]. The

• of nonsymmetric cryptands by two sequential double Ugi-4CR-based macrocyclizations (Scheme 28). The approach also relies on MiBs strategy [45]. The main focus was on the use of the Ugi four-component reaction (Ugi-4CR) due to the tremendous capability of this process to generate molecular complexity

Easy, efficient and versatile one-pot synthesis of Janus-type-substituted fullerenols

• Marius Kunkel and
• Sebastian Polarz

Beilstein J. Org. Chem. 2019, 15, 901–905, doi:10.3762/bjoc.15.87

• amphiphile with dimethoxyaniline as substituent (all characterization data can be found in Supporting Information File 1). ESIMS (Figure 1a) shows a rather complex fragmentation pattern similar to unsubstituted fullerenol compounds known in the literature [33]. The general complexity of the spectrum derives

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• ]. Several reliable approaches to produce cyclopropanols have been reported in the literature (Scheme 1) [6] but a number of challenges still exist particularly for the stereoselective preparation of cyclopropanols of high structural complexity and substitution pattern. Since the first synthesis of

• hydrolyzed carbometalated products with compounds already described in the literature [83]. To further increase the structural complexity of the final cyclopropanols, we also tested the reaction on nonfunctionalized trisubstituted cyclopropenes (6c–g). Addition of primary alkyl- or arylcuprates followed by

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• , eight sesquiterpenoids (1–8), belonging to four different structural types, were isolated from two South China Sea soft corals (C. viridis and L. flava) for the first time. The discovery of these metabolites extended the structural diversity and complexity of sesquiterpenoids derived from soft corals C

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• of higher complexity by employing simpler, more efficient, catalytic methods that are also environmentally friendly. Molecular hybridization has emerged as an interesting strategy for the synthesis of bioactive molecules with improved properties by combining two or more pharmacophore fragments in a

Polyaminoazide mixtures for the synthesis of pH-responsive calixarene nanosponges

• Antonella Di Vincenzo,
• Antonio Palumbo Piccionello,
• Alberto Spinella,
• Delia Chillura Martino,
• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2019, 15, 633–641, doi:10.3762/bjoc.15.59

• providing no separation of the components. The mixtures were adequately characterized by means of combined HR-ESIMS, FTIR and NMR techniques and, despite their complexity, they were successfully used to accomplish the subsequent preparation of pH-sensitive calixarene hyper-reticulated nanosponge materials

• features as those of I; however, because of the greater complexity of the mixture, and of the structures of the compounds present in it as well, the spectra in general show a much worse resolution of the signals. As a final remark, it is worth mentioning here that integration analysis of the signals in the

• 1H NMR spectra of our mixtures cannot be considered enough unreliable, unfortunately, because of both the complexity of the partly overlapped signals pattern, and the concomitant overlap with the signals relevant to the solvent (DMSO and residual water). Synthesis and characterization of the CaNS

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• respect to their complexity (Figure 1), these classical metabolic engineering approaches can be classified as level 1 efforts, i.e., the optimization of a natural pathway in a native organism, or level 2 efforts, i.e., the transplantation or reconstruction of a natural pathway in a new host organism [11

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• exemplify the complexity levels that can be achieved with this approach, we list two multiple MCRs showing their power to reach very elaborate scaffolds with several diversity points in short sequences. Westermann described a remarkable Ugi/Ugi–Smiles protocol using a carboxylic acid provided with a phenol

• antitumor peptidomimetics (Scheme 16) [53]. The convergent approach employs three different isocyanide-MCRs, efficiently prepares the building blocks and combines them, intercalating protecting group cleavages. Conclusion The MMCRs approach represents the most efficient way to build chemical complexity and

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• -pot procedure with one purification step), much better yields, no need of expensive catalysts as in ring-closing metathesis (RCM) reaction and higher complexity/diversity on the macrocyclic ring, e.g., insertion of heteroatoms that could improve the ADMET properties (Scheme 1) [4]. Results and

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• ] of norbornene derivatives with a suitably located alkynyl side-chain on the nucleus (path 2, Scheme 1) to form carbocycles has been less explored. The greatest advantage of this protocol lies in its potential in increasing the molecular complexity through Diels–Alder reaction of the resulting ring

Carbonylonium ions: the onium ions of the carbonyl group

• Daniel Blanco-Ania and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2018, 14, 2568–2571, doi:10.3762/bjoc.14.233

• proceed then to propose a precise and usable term for describing intermediates 1 after having demonstrated that the names used in the literature are inaccurate. Modern nomenclature is able to name and describe every single canonical form of any compound independently of the complexity of the intermediate

• . Applying systematic nomenclature to intermediates 1 would generate the cumbersome names “organylidene oxonium ions” or “organylidene oxidanium ions” [34]. Clearly, the length and complexity of these names would prevent researchers from using them. Another alternative would be to combine the terms “carbene

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

• Antonio Arcadi,
• Sandro Cacchi,
• Giancarlo Fabrizi,
• Francesca Ghirga,
• Antonella Goggiamani,
• Antonia Iazzetti and
• Fabio Marinelli

Beilstein J. Org. Chem. 2018, 14, 2411–2417, doi:10.3762/bjoc.14.218

• product (Table 1, entry 10). Products substituted in the indole and quinazoline frameworks were also obtained (Table 1, entries 12–16). It is worth noting that the reaction tolerates a -Br substituent (Table 1, entries 8 and 16) which may serve as a useful handle for increasing molecular complexity

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

• effort to reduce the complexity of the NMR spectra observed for the diastereomeric onchidal–pyrrole adducts, a range of simpler achiral n-pentyl 11–14 and cyclohexylmethyl 15–18 side-chained model compounds, as either the dialdehyde or masked dialdehyde variants, were prepared (Figure 2). Horner

Dynamic light scattering studies of the effects of salts on the diffusivity of cationic and anionic cavitands

• Anthony Wishard and
• Bruce C. Gibb

Beilstein J. Org. Chem. 2018, 14, 2212–2219, doi:10.3762/bjoc.14.195

• and I− to induce substantial aggregation. The data for the I− salts illustrate a further complexity to the ability of salts to induce precipitation of ammonium ions such as 2. Thus, although the aggregation induced by KI and CsI are not significantly different, there is a trend for cation-induced

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• chemical calculations were done in several steps: selection of optimal conformers; organization of initial complex geometry; complex optimization procedure. The conformers search procedure has been done only for calix[4]arene’s triazolyl substituents due to complexity of the whole molecule. Conformers of

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• presenting and evaluating various approaches for building a unified multistep synthesis platform in Table 3 we have given definitions of a few terms used throughout the manuscript and their relevance. Design complexity A general flow chemistry setup requires some basic equipment like pumps, reactors (usually

• volume in the overall system. This would enhance the residence time, demand more safety features and also need more inventory. A larger dead volume has its own challenges. Control strategy: Devising a control strategy for a unified synthesis platform itself will be the most complex task. The complexity

Host–guest complexes of conformationally flexible C-hexyl-2-bromoresorcinarene and aromatic N-oxides: solid-state, solution and computational studies

• Rakesh Puttreddy,
• Ngong Kodiah Beyeh,
• S. Maryamdokht Taimoory,
• Daniel Meister,
• John F. Trant and
• Kari Rissanen

Beilstein J. Org. Chem. 2018, 14, 1723–1733, doi:10.3762/bjoc.14.146

• understanding of the particular interactions is required. The N-oxide oxygen atoms potential to act as a HB acceptor for multiple simultaneous N–O···(O–H)host interactions raises the molecular complexity. These are the dominant non-covalent interactions, in both the solid and solution state, compared to endo

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• organic compounds are, like all natural products/secondary metabolites, staggeringly diverse with respect to their natural source and their level of structural complexity. As part of their molecular architecture, sulfur can appear in the form of various functional groups and oxidation states: thiol

• of the optically active 1,5-benzothiazepines has been done by Lévai and Kiss-Szikszai [103]. Conclusion Sulfur, with its ability to exist in various oxidation states and thus various combinations with other atoms, introduces additional intriguing complexity to the molecular architecture of natural

The phenyl vinyl ether–methanol complex: a model system for quantum chemistry benchmarking

• Dominic Bernhard,
• Fabian Dietrich,
• Mariyam Fatima,
• Cristóbal Pérez,
• Hannes C. Gottschalk,
• Axel Wuttke,
• Ricardo A. Mata,
• Martin A. Suhm,
• Melanie Schnell and
• Markus Gerhards

Beilstein J. Org. Chem. 2018, 14, 1642–1654, doi:10.3762/bjoc.14.140

• -spectroscopic study to mixed aromatic olefinic ethers: in the case of phenyl vinyl ether (PVE), there is an ethenyl moiety replacing one of the phenyl rings compared to DPE. This introduces a localized π system along with the delocalized phenyl π system as hydrogen bond acceptor sites. Thereby, the complexity

A conformationally adaptive macrocycle: conformational complexity and host–guest chemistry of zorb[4]arene

• Liu-Pan Yang,
• Song-Bo Lu,
• Arto Valkonen,
• Fangfang Pan,
• Kari Rissanen and
• Wei Jiang

Beilstein J. Org. Chem. 2018, 14, 1570–1577, doi:10.3762/bjoc.14.134