Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• double labeling of the mRNA cap with alkyne moieties could also be achieved based on a recently reported enzymatic cascade reaction [99]. In this system a Se-propargyl-modified AdoMet analogue (SeAdoYn [100]) was prepared enzymatically from the respective methionine analogue and ATP by a methionine

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• , regenerating the trifluoromethyl radical in the process, was also considered. Intermediate 2 was ultimately converted into the final product after liberating an acetyl cation, which was captured by a chloride anion to give acetyl chloride (Scheme 3). Trifluoromethylation of olefins with cascade reactions: The

• most widely described type of reactions in which CF3SO2Cl and molecules carrying a C=C double bond are involved are actually cascade reactions that include a cyclisation or a group migration step. In this context, the acrylamide motif was a notably popular object of research, and served in several

• was obtained predominantly: the α-aryl-β-trifluoromethyl amide 6. This compound was determined to be issued from a trifluoromethylation/1,4-aryl shift/desulfonylation cascade reaction (Scheme 7). This reaction could be performed on various N-aryl,N-tosylacrylamides with moderate to good yields. The

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• Scheme 10. β-Trifluoromethyl ketones could also be obtained from allylic alcohols 25 by a cascade trifluoromethylation/1,2-aryl migration. Yang, Xia and co-workers employed sodium triflinate under metal-free conditions with ammonium persulfate as the oxidant that was necessary to generate the CF3 radical

• (Scheme 11) [30]. Amino- and azotrifluoromethylation of alkenes: Alkene trifluoromethylation was applied to the construction of indole, pyrazole and pyridazinone moieties via a multicomponent cascade reaction developed by Antonchick and Matcha in 2014 [31]. The method was based on the reaction between

• . Notably, diethyl 2,2-diallylmalonate as a diene gave the cyclised product resulting of a radical cascade. It has to be noticed that the reactions were conducted in the presence of 2 equivalents of trifluoroacetic or p-toluenesulfonic acid; yet, there was no mention of hydrotrifluoromethylated side

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• enables uropathogenic Escherichia coli (UPEC) to adhere to urothelial host cells [33][34], which represents the first and most critical step in UTI, triggering a cascade of pathogenic processes ultimately leading to infection. The ligand on urothelial cells binding to the N-terminal lectin domain of FimH

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• University, Miklukho-Maklaya St., 6, Moscow 117198, Russian Federation 10.3762/bjoc.13.252 Abstract The novel cascade two-stage reaction between itaconimides and 1,2-diamino-4-phenylimidazole proceeds regio- and chemoselectively to form tetrahydroimidazo[1,5-b]pyridazines and includes nucleophilic C

• -addition by the activated C=C double bond and subsequent intramolecular recyclization of the intermediate with the amino group involved. Keywords: cascade reaction; diaminoimidazoles; HPLC–HRESIMS; imidazo[1,5-b]pyridazines; itaconimides; Introduction Among the numerous bicyclic fused imidazole

• multiplet (3.17–3.25 ppm). The addition of trifluoroacetic acid did not have a significant effect on the position of the signals of these protons. Thus, the reaction of itaconimides 1 with diaminoimidazole 4 is a regioselective and chemoselective cascade process involving an initial C-addition of

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• -bromooxime 26 with lithium enolate 27 to give oxime 28 via the Michael addition to transient nitrosoalkene NSA6 [31]. Oxime adduct 28 existed predominantly in a cyclic 1,2-oxazine form (Scheme 11). Subsequent benzylation of oxime 28 and the thermal retro-[2 + 2]/[4 + 2]-cycloaddition cascade followed by

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• demonstrate the regiochemistry of the reaction. These cascade reactions proceed first through a Michael addition of the primary amine on the enone, followed by an intramolecular cyclization by the pyridine/pyrimidine nucleus. Unfortunately, no crystal structure could be obtained for the imidazopyrimidines and

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

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• , N-alkylcarboxyspiropyrans have been tagged (via ester or amide linkage) to carbon nanotubes (e.g., for photocontrolled Zn2+ delivery in biological media [8]) and gold electrodes (for photoswitching the bioelectrocatalytic cascade of cytochrome c/cytochrome oxidase [9]), and attachment to

Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol

• Lina Jia and
• Fuzhong Han

Beilstein J. Org. Chem. 2017, 13, 1425–1429, doi:10.3762/bjoc.13.139

• phthalides in good to excellent yields. Conclusion: A concise and efficient synthesis strategy of 3-substituted phthalides from 2-formylbenzoic acid and β-keto acids via a catalytic one-pot cascade reaction in glycerol has been accomplished. Keywords: β-keto acid; decarboxylation; glycerol; one-pot cascade

• [3][4][5], exhibit a broad spectrum of pharmacological activity, such as antibacterial, anti-HIV, antifungal, antibiotic, antitumor and immunosuppressive effects [6][7][8][9][10]. In addition, the one-pot cascade transformation has proven to be the key step in organic syntheses because of its broad

• functional group compatibility and ingenious construction of molecular architectures [11][12][13][14]. Consequently, an efficient synthesis of 3-substituted phthalides via a one-pot cascade reaction is still in high demand. An analogous approach was described involving a catalytic sequence of the aldol

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• spirocyclopentaneoxindoles. Keywords: asymmetric synthesis; four consecutive stereocenters; Michael–Henry cascade reactions; spirocyclopentaneoxindoles; thioureas; Introduction The spirocyclic oxindole core represents an important scaffold that is encountered frequently in many biologically active molecules and natural

• functionalized nitrovinylacetamides are rare. Chiral thioureas [28][38][39] have evolved as powerful hydrogen bonding catalysts for the asymmetric synthesis of spirocyclopentaneoxindoles, which have been demonstrated as acceptable but still considerably limited. Organocatalytic iminium–enamine cascade reactions

• [35] (Scheme 1, reaction 1A) and Michael–Henry cascade reactions [25] (Scheme 1, reaction 1B) reported by Barbas III's group involve the cyclization between α,β-unsaturated aldehydes and nitrostyrenes with 3-substituted oxindoles to generate the corresponding CHO- or NO2-substituted spirooxindole

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

• practical synthetic methods for the selective synthesis of precursor dialkynes bearing different substituents (alkyl, aryl) at the triple bonds, based on ketals or an imine as protecting groups. We show for isomeric dialkynes that the reaction cascade induced by Pt(II) includes ring annulation, sulphur

• all atoms of the starting material are found in the product, and thus fulfil an important requirement of “green chemistry” [31]. However, a different Pt(II)-catalysed reaction cascade was observed for 4c, with adamantyl groups at the alkynes. Here, the annulation step is followed by a C–H bond

• into the functional group it next reacts with. The intermediate D can be regarded as the common precursor for the parallel formation of the observed products, 23 by dissociation from the Pt catalyst and proton migration from the sulfonamide to the alcoholate, and 22 by a cascade of electron movements

G-Protein coupled receptors: answers from simulations

• Timothy Clark

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

• the G-protein. On activation, bound guanosine diphosphate (GDP) in the G-protein is replaced by the triphosphate (GTP) and the α-subunit separates from β/γ. The separated G-protein subunits migrate to effectors in the nearby membrane, where GTP is hydrolyzed to GDP and the signaling cascade initiated

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• of the substrate coordinating cavity. Recently reported targeted engineering [51] of the Class I taxadiene synthase from Taxus brevifolia (TXS) enabled new understanding of the mechanistic procedures that are carried out by this enzyme on the substrate GGPP. Quenching the carbocation cascade that

• deprotonation of a cembrene-15-yl cation intermediate in the cyclization mechanism of TXS leading to the monocyclic cembrene A [51] (Scheme 2). Hence reprogramming the catalytic cascade of diterpene synthases and subsequent functional expression of enzyme variants in a microbial host can not only provide

• labda-13-en-8-yl diphosphate carbocation intermediate and the formation of halima-5(10),13-dienyl diphosphate (Scheme 2). In wild-type Class II diterpene synthases, the labda-13-en-8-yl diphosphate carbocation undergoes either single deprotonation or a cascade of hydride and methyl group shifts prior to

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

• Yan Chen Xiaoman Wang Junchang Wang You Yang Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China 10.3762/bjoc.13.79 Abstract A [4 + 3] synthesis of D-manno-heptulose is described. The cascade

• aldol/hemiketalization reaction of a C4 aldehyde with a C3 ketone provides the differentially protected ketoheptose building block, which can be further reacted to furnish target D-manno-heptulose. Keywords: aldol reaction; cascade reaction; D-manno-heptulose; higher-carbon sugar; ketoheptose

• of the differentially protected ketoheptose building block 2. The ketoheptose 2 can be further divided into C4 aldehyde 3 and C3 ketone 4 via a cascade aldol/hemiketalization pathway. Results and Discussion The synthesis of the C4 aldehyde commenced with commercially available D-lyxose (5, Scheme 2

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• enantioselectively delivered oxabicyclo[4.3.0]nonanes [17]; the Lautens and Lan groups have also contributed to the further development of this reaction [18][19]. The Rovis group employed cyclohexadienone hydroperoxides in a chiral phosphoric acid-catalyzed [1,2]/[1,4]-addition cascade [20]. The same group also

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• thiazole-2-thiones 3 through the thermal cyclocondensation of N-propargylamines 1 with carbon disulfide as developed by Batty and Weedon [75]. (a) One-pot synthesis of 2-benzylthiazolo[3,2-a]benzimidazoles 6 through a base-catalyzed cascade reaction of internal N-propargylamines 4 and CS2. (b) Synthesis of

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• in boldface and colored blue. (B) Chemical structures of acyl homoserine lactones. The acyl side chains are shown in boldface. (A) Schematic representation of the signal transduction cascade of quorum sensing stimulated by the ComX pheromone in B. subtilis. (B) Amino acid sequences of the aspartate

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• the Passerini α-acyloxycarboxamide adduct 12 [18]. Tandem reactions Tandem reactions (also known as cascade [22] or domino reactions [23]) are chemical transformations that involve at least two independent reactions utilizing different functional groups with distinct chemical reactivities [24][25][26

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• by OxyE, which acts between OxyB and OxyA in the cyclisation cascade [27]. In vivo experiments also hinted towards the activity of the Oxy enzymes against the substrate peptides whilst they remain bound to the NRPS [29], and in vitro experiments performed with OxyB from the vancomycin biosynthesis

• only some of the mechanistic features of the OxyA reaction but also the role of the X-domain on the activity of this enzyme and to determine whether the recruitment domain can also affect peptide selectivity for later Oxy enzymes in the GPA cyclisation cascade. Results and Discussion Spectral analysis

• and the other free in solution [12]. Studies on the biosynthesis of teicoplanin and the vancomycin-type chloroeremomycin GPA showed decreasing affinity of the P450s to the X-domain with later positions in the GPA cyclisation cascade [13][16], and our results from the A47934 system would appear to

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Olga C. Dennehy,
• Valérie M. Y. Cacheux,
• Benjamin J. Deadman,
• Denis Lynch,
• Stuart G. Collins,
• Humphrey A. Moynihan and
• Anita R. Maguire

Beilstein J. Org. Chem. 2016, 12, 2511–2522, doi:10.3762/bjoc.12.246

• key α-thio-β-chloroacrylamide casade as a continuous flow reaction on a multi-gram scale is described, while the tuneable nature of the cascade, facilitated by continuous processing, is highlighted by selective generation of established intermediates and byproducts. Keywords: α-thio-β

• -chloroacrylamides; cascade reactions; flow chemistry; Introduction Since the efficient and highly stereoselective transformation of α-thioamides to the corresponding α-thio-β-chloroacrylamides derivatives was first reported [1][2], the considerable synthetic utility of these heavily functionalized acrylamide

• ready access to appreciable quantities of material is required. Preparation of α-thio-β-chloroacrylamides typically results from a three-step synthetic route, culminating in a final cascade/domino reaction [13] where a toluene solution of α-thioamide and NCS is subjected to a ‘hot plunge’ by placing it

Methylenelactide: vinyl polymerization and spatial reactivity effects

• Judita Britner and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 2378–2389, doi:10.3762/bjoc.12.232

• also shows additional postulated radical reactions including the formation of a bicyclic lactide radical to initiate the main polymerization. Since the spontaneous homolytically C–H cleavage may represent the first step in the reaction cascade, theoretical calculations on a DFT level were conducted

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• a RY dimer [9]. The substrate is ionised by diphosphate abstraction and the resulting allyl cation undergoes a domino reaction via a series of cationic intermediates and a final deprotonation or attack of water to yield a terpene hydrocarbon or alcohol. This reaction cascade proceeds in a

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• , it has to be noted that the trans-THF was not directly formed in an oxidative cyclization reaction but rather through a subsequent sequential solvolysis/hydride shift/intramolecular reduction cascade. Another total synthesis of cis-sylvaticin (40) has been published by Brown and co-workers in 2008

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• diastereoselective cascade reaction [23]. The crucial stage of the described transformation is the formation of a pyran-4-carboxamide intermediate. A trace amount of it was isolated accidentally and we could not repeat this procedure and characterize the compound by spectra. Results and Discussion In continuation of

• , depending on the substituent R3, and the signals of other appropriate alkyl and aryl substituents. There are two cascade mechanisms that could be proposed for the 3,4-dihydro-2H-pyran-4-carboxamides 2 formation (Scheme 3). Both mechanisms apparently start from the interaction of ketonitrile 1 with aldehyde