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

• the C–C bond between the atoms bearing the OH and NH groups (ring enlargement). The result is an isomerisation of 4a and 4b to form tricyclic compounds 7 containing a nine-membered carbocyclic ring (Scheme 3a) [27]. Isomerisations are the best examples for a perfect “atom economy” [28][29][30] since

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• reagent. The reaction temperature and residence time are 80 °C and 3.5 min, respectively. This product further undergoes a coupling reaction in a packed column containing polymer-supported [bis(trifluoroacetoxy)iodo]benzene (PS-PIFA), which yields a seven-membered tricyclic intermediate with 50% yield

• . The tricyclic intermediate is further mixed with MeOH and water (4:1) and passed through a packed column containing a polymer-supported base at 35 °C. The target compound (±)-oxomaritidine was obtained in 40% yield. The block diagram of different steps performed in this synthesis is shown in Figure 6A

• (trifluoroacetoxy)iodo]benzene as packing material. The control strategy for the packed bed reactor will be similar as discussed earlier. The process stream containing the tricyclic intermediate can be cooled to 35 °C by mixing a cold stream of MeOH/water at the desired mole ratio using a ratio controller. The

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

• naturally leads to the formation of tricyclic taxadiene [56] was achieved by exchanging a valin in position 584 with methionine. The resulting product was identified as a bicyclic diterpene of the verticillene type [51] (Scheme 2). A single residue switch in position 753 (W753H) presumably causes premature

• side: The natural product of wild-type cyclooctat-9-en-7-ol-synthase (CotB2) is a tricyclic diterpene whereas mutations in positions 107 and 288 yield in monocyclic cembrene A and bicyclic 3,7,18-dolabellatriene [57]. Changing the main product specificity of taxadiene synthase from Taxus brevifolia

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

• nucleophilic group were appended to the para-quinol, it would be possible to construct a 5–6–5 fused ring system. Indeed, when R = CH2CH2NHBoc (1f), the desired tricyclic product 2f was obtained. In all cases only a single diastereomer was observed. In a substrate where a β-methyl group is present on the

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

• 7, 20131 Milano, Italy 10.3762/bjoc.13.70 Abstract Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion complexes with β-cyclodextrin (β-CD) in the solid state and in water solution. Rotating frame NOE experiments (ROESY) showed the same geometry of inclusion for both 1

• explicit water to study the inclusion complexes of two tricyclic aromatic molecules – cyclobenzaprine (1) and amitriptyline (2, Figure 1) – with β-cyclodextrin (β-CD). Previous work already considered certain aspects of the interaction of 2 with β-CD [3][4][5][6][7][8], but no full characterization of the

• any disorder: this finding is largely predictable for the rigid tricyclic moiety of 1 but it is remarkable in 2. Indeed, literature data on isolated amitriptyline point out that the fused ring system of 2 shows conformational transitions [10], especially those involving the torsion about the C9–C10

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

• tricyclic skeleton that bears a newly formed pyrrolidine, similar to proline. The post-translational dimethylallylation of two tryptophan residues of a cyclic peptide, kawaguchipeptin A, from cyanobacteria has also been reported. Interestingly, the modified tryptophan residues of kawaguchipeptin A have the

• either a geranyl or farnesyl group at the gamma position to form tricyclic skeleton that bears a newly formed pyrrolidine, which is similar to proline (Figure 3A) [26][27][28]. The posttranslational modification of ComX pheromones with an isoprenoid plays an essential role for specific quorum sensing

• configurations of the tricyclic core scaffold were essential and more critical for its pheromonal activity than the amino acid sequence of the ComXRO-E-2 pheromone [29][30][31][32]. In addition, a previous study using a conditioned medium with Bacillus strains suggested that the chemical structure of the

Characterization of the synthetic cannabinoid MDMB-CHMCZCA

• Carina Weber,
• Stefan Pusch,
• Dieter Schollmeyer,
• Sascha Münster-Müller,
• Michael Pütz and
• Till Opatz

Beilstein J. Org. Chem. 2016, 12, 2808–2815, doi:10.3762/bjoc.12.279

• -alkylated carbazole instead of an indole core. Carbazoles are the core structures of an emerging group of cannabimimetics [11][12]. Several N-alkylated carbazole-3-carboxamides were patented by Diaz, Diaz, and Petrov in 2012 as tricyclic cannabinoid receptor modulators, explored against neuropathic pain [13

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• -allylated product 3j in 12% yield, along with the tricyclic compound 6j, in good yield, which is resulting from the intramolecular conjugate addition of 3j carbanion on the enone moiety (Table 3, entry 2). Under the same conditions, the keto ester 2j reacted with alcohol 1a, in DMF at 80 °C for 6 h longer

• reaction time, to selectively afford the compound 6j in 76% yield (Table 3, entry 3). A plausible reaction mechanism for the formation of the tricyclic compound 6j from the MBH alcohol 1a is presented in Scheme 2. We believe that the treatment of the MBH alcohol 1a with Et3B in the presence of Pd(OAc)2 may

• generate a π-allylpalladium intermediate I that further undergoes a nucleophilic substitution reaction with the β-keto ester carbanion derived from 2j, affording the monoallylated compound 3j. The conversion of the keto ester 3j into the tricyclic product 6j was further performed through an intramolecular

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

• against herbivores. The first total synthesis of leucosceptroid B (105b) was established in 2013 by Huang et al. [167] and two other total syntheses of leucosceptroids A (105a) and B (105b) followed two years later [168][169]. The common tricyclic core structure of the natural products had already been

• oxidative cyclization catalyzed by Ru(VII) yielded THF diol 102 in 55% yield as a single diastereoisomer, without considering the configuration of the protected alcohol, as this position was subsequently oxidized to enable a Sonogashira cross-coupling to access 103. The tricyclic core structure 104 could be

Thiophene-forming one-pot synthesis of three thienyl-bridged oligophenothiazines and their electronic properties

• Dominik Urselmann,
• Konstantin Deilhof,
• Bernhard Mayer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2016, 12, 2055–2064, doi:10.3762/bjoc.12.194

• electronics [37][38][39][40]. In comparison to thiophene, phenothiazine, a tricyclic dibenzo-1,4-thiazine, possesses a significantly lower oxidation potential, similar to aniline. However, phenothiazine derivatives form stable deeply colored radical cations with perfect Nernstian reversibility [41][42][43][44

Application of heterocyclic aldehydes as components in Ugi–Smiles couplings

• Katelynn M. Mason,
• Michael S. Meyers,
• Abbie M. Fox and
• Sarah B. Luesse

Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191

• step from achiral starting materials, producing two diastereomeric exo products that feature rigid tricyclic cores. Lone Ugi–Smiles adducts 2 were not isolated for any reactions that used a substituted 2-furaldehyde component. However, generation of adduct 1 can be rationalized as an Ugi–Smiles

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• ), five methine (CH) and one additional quarternary carbon, supporting a tricyclic structure (Table 2). The 1H,1H-COSY spectrum revealed three spin systems C2-3, C7-8-9-14, and C12-11-13 (Figure 2c) and the HMBC spectrum showed cross peaks between H-15 and C-3, C-4 and C-5, and between H-12/H-13 and C-11

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

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

• be obtained by spontaneous or enzyme-supported hemiacetalisation followed by dehydration [34]. The tricyclic core unit is oxidised further and heavily decorated by tailoring enzymes, also involving an unusual rearrangement leading to the dioxane unit, whose carbon atoms originally derive from a sugar

• most interesting that the branching KS domain alone mediates the entire catalytic sequence and represents a unique family of ligase-cyclase. 1.6.3 Favorskii rearrangement: Enterocin. Another mechanism applies for the δ-lactone embedded in the tricyclic, caged core of the bacteriostatic agent enterocin

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

• , etc. As we shall see, a structure akin to 35 would accomplish this. In searching for another structure that accomplishes this we discovered tricyclic 32. The transition state that converts 28 into 32 is 31. For the C8F8 complex, 28, the Pt–C distances are 2.08 Å. In 31 the corresponding distances are

• . It is easy to see the electronic basis for ring folding and construction of the tricyclic molecule. Consider that in 28 the filled ML2 b2 orbital coordinates to the two lower p AOs in the upper component of e2u in Figure 8a. Then empty a1 interacts with the lower component in Figure 8a. As ML2 slips

• important consequence of this motion is that the p AO on the opposite side of the ring in 34 has the correct phase to generate a C–C σ bond and this collapses to bicyclic 32. Our calculations find that C8F8–Pt(dpe) will be caught in the deep potential energy well of the tricyclic isomer, 32. Hughes and co

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• transferase (ComQ), which transfers an isoprenyl group to position 3 of the indole side chain of a conserved tryptophan residue [135]. This directly generates a tricyclic structure, presumably via attack of the main chain amide nitrogen onto the iminium intermediate that is generated following prenylation

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• -catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred

• ketones 3–6 that led to tricyclic compounds. Methyl ketone 1 provided under the reaction conditions (2 mol % Pd(PPh3)4, 3.5 equivalents NEt3, DMF, 110 °C, 3 d) that had been optimized with compound 4 a moderate yield of the tetralin derivative 7 formed as a single diastereomer (Scheme 3). Although the

• with those discussed below, where X-ray crystal structure analyses unequivocally confirmed the relative configurations of cyclization products. With the cyclic ketones in part considerably higher yields of tricyclic products could be obtained (Schemes 4–6). The cyclopentanone derivative 3 (Scheme 4

Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

• Lucian G. Bahrin,
• Henning Hopf,
• Peter G. Jones,
• Laura G. Sarbu,
• Cornelia Babii,
• Alina C. Mihai,
• Marius Stefan and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2016, 12, 1065–1071, doi:10.3762/bjoc.12.100

• –activity relationship study concerning the antibacterial properties of several halogen-substituted tricyclic sulfur-containing flavonoids has been performed. The compounds have been synthesized by cyclocondensation of the corresponding 3-dithiocarbamic flavanones under acidic conditions. The influence of

• class of synthetic tricyclic flavonoids [13]. Given the promising results that have been obtained for compound 1 (Figure 1), we chose this compound for a structure–activity study. For this purpose we initially decided to retain the halogen substituents of the aromatic A and B rings, while changing the

• and 4f crystals suitable for single crystal X-ray analysis were obtained and the results are discussed in the X-ray analysis section. The acid-catalyzed cyclocondensation of flavanones 4a–m afforded the tricyclic flavonoids 5a–m in good yields [23] (Scheme 1). The formation of the 1,3-dithiolium ring

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• oxidative coupling sequence (Scheme 48). Similarly, the tricyclic N-heterocyclic core in natural (+)-asperazine and idiospermuline was also efficiently synthesized in 71% overall yield. The oxindole was reduced to the lactol by NaBH4, which was then subjected to a camphorsulfonic acid (CSA)-promoted

• cyclization, giving the tricyclic N-heterocyclic core. Very recently, Shi and co-workers reported the chiral phosphoric acid (CPA, cat. 31)-catalyzed asymmetric dearomatization reactions of tryptamines with 3-indolyl-3-hydroxyoxindoles, affording the indole-containing tricyclic N-heterocycles in a highly

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• an MIC value of 16 μg mL−1. Further bioactivity assays were impossible to carry out due to the minute amounts in which this metabolite is produced. Consequently, a synthetic approach has been utilized in order to overcome this problem, leading so far to the synthesis of the tricyclic core structure

• degradation of a sterol, leading to the tricyclic core structure. Compounds 27 and 30 have shown inhibitory activity towards A. crystallopoietes (MIC value of 8 and 4 μg mL−1, respectively). Since salimabromide is a novel structure of putatively assigned PKS origin, our research group sequenced the genome of

A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

• Oksana S. Mikhalchenko,
• Dina V. Korchagina,
• Konstantin P. Volcho and
• Nariman F. Salakhutdinov

Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64

• reaction products unexpectedly decreased, and the yield of fluorinated product 8f was only 20%. In addition to the expected products 2f and 8f, tricyclic compound 9f with an epoxychromene scaffold was isolated from the reaction mixture (Scheme 3), whose formation was previously observed only when using K10

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• desired products in excellent yields and selectivities. In order to broaden the utility of this methodology, the authors reduced the nitro group to an amine. The product was in situ transformed to the tricyclic product 102, through a diastereoselective reductive amination, that controlled the

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• -formylindoles 98 and nitroolefins 41 to generate the corresponding tricyclic adducts 99 using cupreidine derivative CPD-30 (Scheme 23). Although the substrate scope for the enantioselective reaction is limited, the diastereoselectivities are reasonable, and the enantioselectivities are excellent. Other

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

• which provided the hydrogenated tricyclic cyclopenta[f]indole core system in high yield. Keywords: gold-catalyzed reactions; heterocycles; indole alkaloids; natural products; synthesis; Introduction The raputindoles (1, raputindole A, Figure 1) from the rutaceous tree Raputia simulans Kallunki

• constitute a unique group of terpenoid bisindole natural products [1] sharing a linear cyclopenta[f]indole tricyclic partial structure. The cyclopenta[f]indole system also occurs as partial structure of the nodulisporic acids [2], the shearinines [3][4][5][6] and janthitrems [7][8][9][10]. While work has

• SnCl4-induced cyclization afforded the desilylated tetracyclic indeno[1,2-f]indoline 41 in high yield (82%). We did not detect any regioisomer, probably because the TIPS group was still in place in the regioselecting step. In order to obtain a tricyclic cyclopentaindoline, the propargylic alcohol 43 (96

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• extract led to the isolation of a new tricyclic macrolactam named tripartilactam (24) [103]. Tripartilactam (24) contains an unprecedented cyclobutane moiety, which links the 8- and 18-membered rings, and it is most likely derived from a photochemically [2 + 2] cycloaddition reaction of the corresponding