Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• usually performed by joining the two phosphate moieties at the end of the multistep synthesis [24][25][26][27][28][29]. Similarly, the preparation of the new cpIMP derivative 4 could be performed by the cyclization of a monophosphate precursor via phosphodiester bond formation. For this purpose we

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• materials or require expensive reagents and a multistep synthesis. The [18F]trifluoromethylation performed with commercially available reagents by using [18F]fluoride demands no complex such as [18F]CF2Cu, and thus the method should contribute to efficient PET imaging [42] (Scheme 8). Synthesis of

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• course among the others. In particular, I enjoyed one course called “Organic Synthesis Skills” taught by Professor Zhixin Huang, which introduced multistep synthesis. I must say that since 1987 I have benefited greatly from this course as a graduate student at the Shanghai Institute of Organic Chemistry

• institution for organic chemistry in China. Studying at SIOC: N···I interaction I joined SIOC in late August of 1987. For many years, graduate students in the first year studied physical organic chemistry, organic synthesis, and organic analytical chemistry. Impressively, all students performed 6–8 multistep

• synthesis experiments that involved the use of all standard organic synthesis techniques. This was a challenge to many students, but all received systematic training in organic synthesis upon completion of the experiments. In 1988, I entered Professor Ching-Sung Chi’s group in the Laboratory of Organic

The simple production of nonsymmetric quaterpyridines through Kröhnke pyridine synthesis

• Isabelle Sasaki,
• Jean-Claude Daran and
• Gérard Commenges

Beilstein J. Org. Chem. 2015, 11, 1781–1785, doi:10.3762/bjoc.11.193

• nonsymmetric quaterpyridines; Constable et al. proposed a multistep synthesis of 4’-(alkylthio)quaterpyridines [23] to avoid the Stille palladium-catalyzed coupling, whereas Fallahpour obtained the 4’-nitroquaterpyridine by employing the Stille coupling method [24]. Sauer et al. extended the use of triazine

• ”’-quaterpyridines was described that required a multistep synthesis producing elaborate intermediates [24][27]. This short survey of the different ways to produce quaterpyridines (and in particular, nonsymmetric quaterpyridines) shows that a new simple synthesis can be quite relevant. The synthetic approach adopted

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• -tert-butyl peroxide [46]. As both methods utilize phosphorus starting materials which are not commercially available and a multistep synthesis is required for their preparation. As with oxaphospholane 4, compound 5 was reacted with 3 equiv of various Grignard reagents to produce phosphine oxides in

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

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• -step of the synthesis of glycozoline 37, an antifungal and antibacterial agent. Analogously, 38 was converted to 39 as a part of the multistep synthesis of two different tetrahydropyrroloiminoquinone alkaloids 40 and 41 (Scheme 15) [58][60]. Tanaka et al. could achieve the electrochemical construction

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• [30]. The lipo-amino acids used previously for synthesis of the LCP system [31] were prepared by a multistep synthesis which resulted in a racemic mixture. In the current study, enantiomerically pure lipidated Fmoc-lysine (8) was synthesized and used to prepare the lipidic adjuvanting moiety

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• of two hydroxy methylene groups present in pentofuranose derivatives with a PEG dimethyl ester yielded sugar-PEG copolymers used for drug encapsulation. The carbohydrate monomer was obtained by a multistep synthesis starting from the easily available diacetone glucose (Scheme 5) [41]. Galactose has

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• hybrid molecules to date. An extensive literature survey revealed the existence of a multistep synthesis with low yields and long reaction times. This encouraged us to develop a new methodology for this synthesis. Results and Discussion Three different approaches for the construction of the proposed 2-(4

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• illustrated by the work of Charette et al. who used this reaction in the first step of a multistep synthesis to produce chiral arylphospholane [54]. Another interesting example, reported by Selikhov et al., involved an AT reaction between a functionalized coumarine and dioleyl phosphite [55]. In this reaction

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• performed with Amberlyst-15 ion-exchange resin. This approach was used in the multistep synthesis of the natural endoperoxide 9,10-dihydroplakortin, which exhibits antimalarial and anticancer activities as do its structural analogues [320][321]. 2-(3,6,6-Trimethyl-1,2-dioxan-3-yl)ethanol (224) was

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

• times and has been used in over 600 publications. Synthesis of Garner’s aldehyde Garner’s aldehyde (1) has been widely used as an intermediate in multistep synthesis. Thus the synthesis of 1 has to meet some essential requirements: 1) easy and large scale preparation and 2) configurational and chemical

• Garner’s aldehyde. BDP - bis(diazaphospholane). Use of Garner’s aldehyde 1 in multistep synthesis. Explanation of the anti- and syn-selectivity in the nucleophilic addition reaction. Herold’s method: (a) Lithium 1-pentadecyne, HMPT, THF, −78 °C (71%); (b) Lithium 1-pentadecyne, ZnBr2, Et2O, −78 °C → rt (87

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• quinone methides 17 and 19. Unexpected phosphonylation of the aromatic nucleus in reactions of quinone methides 19 and 21. Multistep synthesis of trisphosphonate 18 starting from quinone methide 25. Synthesis of hexaethyl methylidynetrisphosphonate (6) via metal-carbenoid-mediated P–H insertion reaction

3D-printed devices for continuous-flow organic chemistry

• Vincenza Dragone,
• Victor Sans,
• Mali H. Rosnes,
• Philip J. Kitson and
• Leroy Cronin

Beilstein J. Org. Chem. 2013, 9, 951–959, doi:10.3762/bjoc.9.109

• of aldehydes and primary amines. Secondly, two reactors were connected in series to first perform an imine synthesis and then subsequently an imine reduction, with this second setup showing the potential for using the 3D-printed devices as reliable tools in multistep synthesis. This showed that the

A one-pot catalyst-free synthesis of functionalized pyrrolo[1,2-a]quinoxaline derivatives from benzene-1,2-diamine, acetylenedicarboxylates and ethyl bromopyruvate

• Mohammad Piltan,
• Loghman Moradi,
• Golaleh Abasi and
• Seyed Amir Zarei

Beilstein J. Org. Chem. 2013, 9, 510–515, doi:10.3762/bjoc.9.55

• )anilines with alkynes to form 4,5-dihydropyrrolo[1,2-a]quinoxalines [23][24]. Kobayashi and co-workers have described the Lewis acid catalyzed cyclization of 1-(2-isocyanophenyl)pyrroles to give pyrrolo[1,2-a]quinoxalines in good yields; however, the isocyanide substrates required multistep synthesis [25

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• objective of this brief highlight was to exemplify the synthetic efforts that are often hidden behind short papers on functional systems. Quite extensive multistep synthesis has been covered, followed by innovative surface-initiated polymerization and chemoorthogonal dynamic covalent chemistry. The

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

• orthogonality was shown for O-pentenyl versus O-propargyl glycosides by Hotha et al. [17] and for S-glycosyl O-methyl phenylcarbamothioate (SNea) versus thioglycosides/thioimidates by us [18], but still their applicability to multistep synthesis remains to be proven. Working to expand this concept, our group

Synthesis and photooxidation of styrene copolymer bearing camphorquinone pendant groups

• Branislav Husár,
• Norbert Moszner and
• Ivan Lukáč

Beilstein J. Org. Chem. 2012, 8, 337–343, doi:10.3762/bjoc.8.37

• use of a cheaper racemic starting material and by a simplified multistep synthesis. A shorter alternative synthetic route to 6 from 1 was proposed (Scheme 2, see Supporting Information File 1 and Supporting Information File 2 for full experimental data). (±)-10-Iodocamphor (8) was prepared in one step

Efficient oxidation of oleanolic acid derivatives using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP): A convenient 2-step procedure towards 12-oxo-28-carboxylic acid derivatives

• Jorge A. R. Salvador,
• Vânia M. Moreira,
• Rui M. A. Pinto,
• Ana S. Leal and
• José A. Paixão

Beilstein J. Org. Chem. 2012, 8, 164–169, doi:10.3762/bjoc.8.17

• -lactones can be efficiently converted into the corresponding 12-oxo-28-carboxylic acid derivatives by bismuth(III) triflate catalysis [18]. This new approach not only avoids an inconvenient multistep synthesis by means of a protection/deprotection strategy [19][20] but also results in chemical modification

Continuous proline catalysis via leaching of solid proline

• Suzanne M. Opalka,
• Ashley R. Longstreet and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2011, 7, 1671–1679, doi:10.3762/bjoc.7.197

• and can be precisely controlled. In addition, continuous technology enables the generation and immediate use of unstable or hazardous intermediates [4][5][6][7][8][9] as well as the combination of many reactions in series to achieve multistep synthesis [9][10][11][12][13]. Despite the many favorable

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• quantities of the compound and suggested that such a setup can be used for the continuous multistep synthesis of a much wider range of chemical substances. A sequential chemo-enzymatic reaction in continuous flow was also developed by Luckarift and coworkers [40]. Their three-step process comprises reduction

• efficiency of the multistep synthesis of target compounds, due to the dissipation of intermediates in numerous side reactions. The amendment of continuous in vivo coupled-reaction processes by metabolic engineering [59] is a promising technology, which brings into play another crucial biological principle

PEG-embedded KBr₃: A recyclable catalyst for multicomponent coupling reaction for the efficient synthesis of functionalized piperidines

• Sanny Verma,
• Suman L. Jain and
• Bir Sain

Beilstein J. Org. Chem. 2011, 7, 1334–1341, doi:10.3762/bjoc.7.157

• suffer from the drawbacks of multistep synthesis and a lower yield of the desired products. On the other hand, the one-step coupling between an aldehyde, an amine and a 1,3-dicarbonyl compound represents a straightforward approach for their synthesis. Recently, a variety of improved methods employing

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• , CM) as essential transformations in the multistep synthesis of monocyclic iminocyclitols, while also discussing the successes and failures in effecting the above mentioned three critical stages. New perspectives may open up for practitioners of both glyco- and metathesis chemistry involved in the

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• interaction between the above noted proteins and modified oligonucleotides, in which thymidine is replaced by a 5-formyl derivative. A phosphoramidite 145 for oligonucleotide synthesis was prepared from O2-2'-cyclouridine (135) by a multistep synthesis (Scheme 24). In a first step, O2-2'-cyclouridine (135