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

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

• 10a and 11a can lead respectively to the final benzindenes 5a and 6a. Thus, intermediate 11a undergoes a disrotatory 6π-electrocyclic ring closure [49] via the transition structure TS6 to give the tricyclic species 13a. By an analogous electrocyclic ring closure through TS7, compound 10a is converted

• tricyclic intermediates 12a and 13a, the rate determining reaction step is predicted to be the first one, i.e. the initial hydrogen migration, and this study predicts that a [1,9]-H shift is less costly in terms of energy than a [1,5]-H or [1,7]-H one. The more extended conjugation, the lower steric

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• the tricyclic core were controlled via Rh-catalyzed stereoselective C–H insertion and the subsequent reduction from the convex face. Keywords: bifunctional catalysis; hydrogen bonding; organocatalyst; oxa-Michael; prostacyclin; Introduction Prostacyclin (PGI2, Figure 1) is a physiologically active

• clinical application of 1, as well as the development of more active derivatives. Due to the unique tricyclic core of 1, which bears four contiguous stereocenters, various approaches for the synthesis of key intermediate 2 (Scheme 1) have been reported [14][15][16][17][18][19][20][21][22][23], including a

• ) at the ortho position was methyl, or via coupling reactions with C4 units when X was a bromo substituent. The cis-fused tricyclic core of 3 was assumed to be constructed by a stereoselective C–H insertion of diazoester 4, which can be readily prepared from the Weinreb amides 5 or 6 via Claisen

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• ester even under the dilution conditions of an NMR tube (Figure 4). The signal set of boronic ester 7 is significantly shifted compared to the 1H NMR spectra of the educts, because the central δ-valerolactam of the 5,6,5-membered tricyclic fused ring system is locked in the boat conformation. Increasing

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

• Danishefsky. Proposed biosynthesis of plumisclerin A (118). Synthesis of the tricyclic core structure of plumisclerin A by Yao. Total synthesis of 4-hydroxydictyolactone (137) by Williams. Photoisomerization of 4-hydroxydictyolactone (137) to 4-hydroxycrenulide (138). The total synthesis of

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

• incorporation pattern in the tricyclic aromatic moiety suggests a normal PKS assembly line. Moreover, a decarboxylation step is indicated by incorporation of the acetate methyl carbon atom into C-18. In contrast, the origins of C-13 to C-17 remained unclear because of low incorporation of acetate into this part

• -10 excluded a simple mechanistic assembly of the tricyclic system. Instead, advanced NMR experiments focusing on 2JC,C-couplings revealed that C-8 and C-10 originate from the same glucose molecule. To account for this surprising observation, a new mechanistic proposal was suggested involving a carbon

• are in line with the proposed cyclization mechanism starting from geranylfarnesyl diphosphate (GFPP, 53), which undergoes two cyclizations yielding cation 54. A 1,5-hydride shift at C-12 to C-19 leads to the allylic cation 55. Additional ring closure fuses the tricyclic system 56, which rearranges to

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• it may be suspected that the presence of the two chlorine atoms significantly decreased the basicity of the pyridine (Scheme 21). Tricyclic compound 59 was prepared by a RCM of diene 58 that incorporates a quinoline moiety [61]. In this case, a phenyl group was present at C2 and may be responsible

• involving alkenes containing various N-heteroaromatics. Synthesis of dihydroisoquinoline using a RCM. Formation of tricyclic compound 59. RCM in the synthesis of normuscopyridine. Synthesis of macrocycle 64. Synthesis of macrocycles possessing an imidazole group. Retrosynthesis of an analogue of