Naturally occurring tocopherols and tocotrienols are single-isomer vitamin E compounds. (2R,4’R,8’R)-alpha-Tocopherol as a prominent example is of high commercial interest due to its biological and antioxidant properties.^[1] Although the stereospecific cyclization reaction of hydroquinone intermediates and precursors to chromans under carefully controlled acidic conditions is known for a long time^[2] and has been used as a key step in many total syntheses,^[3] the mechanism of this transformation is unknown.

We investigated the course of the acid catalyzed ring closure reaction by starting from doubly ¹⁸O-labelled hydroquinone derivatives obtained by applying standard literature procedures showed complete (>95%) chirality transfer as well as ¹⁸O-incorporation. The mechanism proposed will be discussed in comparison to findings documented in previous research papers.

References:

[1] T. Netscher, Vitamins Hormones 2007, 76, 155-202.
[2] H. Mayer, W. Vetter, J. Metzger, R. Rüegg, O. Isler, Helv. Chim. Acta 1963, 50, 1168-1178; N. Cohen, R. J. Lopresti, C. Neukom, J. Org. Chem. 1981, 46, 2445-2450.
[3] See e.g. C. Rein, P. Demel, R. A. Outten, T. Netscher, B. Breit, Angew. Chem. Int. Ed. 2007, 46, 8670-8673, and references cited therein.

Indoles are important structural motifs found in biological and pharmacological compounds.[1] Therefore, the construction and functionalization of indole skeletons has attracted considerable attention. On the other hand, the use of gold salts has gained a lot of attention in the recent times because of their powerful soft Lewis acidic nature. Such a property allows gold catalysts to activate unsaturated functionalities such as alkynes, alkenes, and allenes, to create C–C bonds under extremely mild conditions.[2] Moreover, Baylis–Hillman (BH) adducts are usually flexible and multifunctional products which can be easily transformed in a huge number of derivatives.[3] However, although many efforts have been made in these fields, the gold-catalyzed reactions using BH adducts derived from formyl-indoles as substrates constitute an unexplored field of noble metal catalysis. In our continuing efforts on the construction of potentially bioactive heterocycles,[4] we wish to report now details of the gold-catalyzed direct synthesis of dihydrocyclopenta[b]indoles from indole-tethered a-hydroxacrylates (Baylis–Hillman adducts) derived from formyl-indoles. The newly formed five-membered ring arises from a selective indole hydroarylation followed by dehydration.

[1] (a) Kaushik,N. K.;Kaushik, N.; Attri, P.; Kumar, N.; Kim, C. H.; Verma, A. K.; Choi, E. H. Molecules 2013, 18, 6620. (b) Vicente, R. Org. Biomol. Chem. 2011, 9, 6469.

[2] (a) Hashmi, A. S. K. Acc. Chem. Res. 2014, 47, 864; (b) Obradors, C.; Echavarren, A. M. Acc. Chem. Res. 2014, 47, 902; (c) Alcaide, B.; Almendros, P. Acc.Chem. Res. 2014, 47, 939.

[3] (a) Wei, Y.; Shi, M. Chem. Rev. 2013, 113, 6659; (b) Liu, T.-Y.; Xiec, M.; Chen, Y.-C. Chem. Soc. Rev. 2012, 41, 4101; (c) Singh, V.; Batra. S. Tetrahedron 2008, 64, 4511.

[4] (a) Alcaide, B.; Almendros, P.; Aragoncillo, C.; Fernández, I.; Gómez-Campillos, G. Chem. Eur. J. 2016, 22, 285; (b) Alcaide, B.; Almendros, P.; Fernández, I.; Martín-Montero, R.; Martínez-Peña, F.; Ruiz, M. P.; Torres, M. R. ACS Catal. 2015, 5, 4842. (c) Alcaide, B.; Almendros, P.; Alonso J.-M.; Fernández, I.; Chemm. Commun. 2012, 48, 6604.

Benzochromenes are one of the most important heterocycle compounds which were used as agrochemicals, biological and anticancer agents [1]. Among the various heterogeneous catalysts, graphene-based polymer nanocomposites due to their unique features were used for the synthesis of these kind of compounds. It is a novel and efficient catalyst for the synthesis of chromene derivatives from aldehydes, malononitrile and barbitoric acid [2]. In this research, a simple method including easy work up and high yields with elimination of organic solvents was reported.

References

 [1] Seyyedi, N., Shirini, F., Langarudi, N., Safarpoor, M., RSC Advances, 6, 44630 – 44640, (2016).

 [2] Wang, L., Lu, X., Lei, S., Song, Y., Journal of Materials Chemistry A, 2, 4491-4509, (2014).

Secondary metabolites obtained from Actinomycetales provide a potential source of many new antibacterial, antitumour, antifungal, antiviral, antiparasitic compounds and others. The majority of discovered substances are widely used as medicines for combating multidrug-resistant Gram-positive and Gram-negative bacterial strains, as well as in veterinary practice, agriculture and industry. Members of the Streptomyces genus are outstanding producers of already known secondary metabolites. In our study we isolated a new metabolite from Streptomyces badius fermentation broth. This compound, 2-acetamido-5-hydroxybenzoic acid (1) was already described in literature, however, not yet discovered as Streptomyces badius product. The compound was firstly isolated from fermentation broth and purified by chromatography methods (ion exchange resin DowexWX40, Solid Phase Extraction C18 Polar Plus; HPLC, dC18). Then, the chemical structure of metabolite was determined by ¹H NMR, ¹³C NMR and 2D homo- and heteronuclear (¹H-¹³C HSQC, ¹H-¹³C HMBC) NMR. The molecular formula of (1), C₉H₉NO₄ was identified by high resolution ESI-MS. The chemical structure was analyzed by the UV and IR methods, as well. Biological activities of 2-acetamido-5-hydroxybenzoic acid were evaluated. The compound shows moderate DD-peptidase 64-575 inhibitory activity as well as antioxidative properties (ABTS radical scavenging). Such chemical moiety may serve as model compound for further modern drug discovery and be a source of active substance in anti-ageing cosmetics.

The research was focused on in silico characterization and in vitro biological testing of the series of the compounds carrying a N-arylpiperazine scaffold. Their in silico investigation was based on the prediction of electronic, steric and lipohydrophilic features. The in vitro inhibitory impact of those molecules on a photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts was evaluated using the Hill reaction. Among the tested N-arylpiperazines, the most promising potential to inhibit the PET was found for 1-[3-(3-ethoxyphenyl- carbamoyl)oxy-2-hydroxypropyl]-4-(3-trifluoromethylphenyl)piperazin-1-ium chloride and 1-[3-(4-ethoxyphenylcarbamoyl)oxy-2-hydroxypropyl]-4-(3-trifluoromethylphenyl)piperazin-1-ium chloride. The current study discussed preliminary structure–photosynthesis-inhibiting activity relationships considering electronic, steric and lipophilic properties.

We report herein the first example of a tetradentate hydrazone structurally studied. The analysis of the conformations of this molecule together with the hydrogen bonding interactions allowed us to investigate the changes experienced by this ligand upon coordination to metal centers.

Nitrocompound in the excited states reacts as a strong electron acceptor. We have examined its behaviour in reaction with a strong electron donors such as ammonia using CASSCF(6,6)/6-311G* and uB3LYP/6-311G* methods. The mechanism of this reaction consists of hydrogen atom transfer from NH₃ to nitrocompound. In the triplet state activation energy is of 21.2 kJ·mol^-1 which is quite low. As a result, there are two radicals being able to interact with other molecules in the system. One possible reaction pathway is NH₂ radicals recombination resulted in hydrazine formation. The second reaction is nitrocompound abstraction of hydrogen atom from ammonia. The product of this reaction will be nitrosomethane. Also, this reaction was investigated by the Bader theory. It shows an opportunity of interaction and electron density localization via the reaction between nitrocompound and amine.

A multicomponent reaction (MCR) can create highly complex molecules from readily available starting materials without the complicated purification operations; thus, MCRs are resource and time-effective and economically favorable processes in diversity generation1. A wide variety of quinazolinone derivatives have been synthesized by condensation of 3-amino- 1, 2, 4-triazole as amine sources, with dimedone and aromatic aldehydes in the presence of 20 mol % of MCM-41-SO3H as effective catalyst in green and reusable catalyst in refluxing DMF conditions through one-pot reactions. Triazoloquinazolinone are important because of their wide range of biological activities, application in medicinal chemistry, pharmaceutical industry and agrochemicals as herbicides and active pharmaceuticals2.

References
1. D. J. Ramon, M. Yus, Angew. Chem. 2005, 44, 1602.
2. V. Haridas, K. Lal, Y. K. Sharma. Tetrahedron Lett. 2007, 48, 4719.

Capsaicin (= (E)-N-(4-hydroxy‐3‐methoxybenzyl)‐8‐methyl‐6‐nonenamide), the natural compound responsible for the spicy flavor in pepper fruits, has shown antioxidant and weight-reductive properties, cardiovascular benefits, anti-carcinogenic activity and recently pain relief effects. Studies on a series of synthetic capsacinoids indicated that the length of alkyl chain affected piquancy, with the possibility of obtaining non‐pungent capsaicin analogues with interesting bioactivieties.¹

We report here on a new efficient procedure for the synthesis of capsaicin analogues, based on the aminolysis of vanillylamine with methyl esters showing structural changes in alkyl chain, catalyzed by the inexpensive and non-toxic triazabicyclo[4.4.0]dec‐5‐ene (TBD).² The procedure is improved by microwave irradiation, which allows to carry out the reaction under solvent-free conditions and to obtain high yields of products. This is an effective and fast procedure for the access to a wide library of capsaicinoids for further biological evaluations, as well as for a large-scale production.

References

1. M.L.Reyes‐Escogido, E. G.Gonzalez‐Mondragon, E.Vazquez‐Tzompantzi, Molecules 2011,16,1253.
2. C. Sabot, K. A. Kumar, S. Meunier, C. Mioskowski, Tetrahedron Lett. 2007, 48, 3863.

In recent years, push-pull π-conjugated systems bearing electron rich (thiophene, pyrrole, furan) and electron deficient heterocycles (pyridine, pyridazine, benzothiazole, etc.) have been widely used as NLO and photochromic materials, metal free organic sensitizers for DSSCs, OLEDs, etc. due to their easy synthesis and efficient tuning of the photophysical properties through small structural modifications.^1-2

During the last decade our research group has published experimental and theoretical results concerning the auxiliary donor/acceptor effect of electron rich and electron deficient heterocycles on p–conjugated systems.² Based on our earlier work we were motivated to extend these studies in order to explore the potential application of a new series of donor-acceptor substituted thienylpyridazines in which the pyridazine heterocycle plays the dual role of p-bridge and acceptor/auxiliary acceptor moiety. Therefore, the pyridazine ring was functionalized in position 3 with different (hetero)aryl-based groups (indole, benzonitrile and nitrophenyl) in order to study the effect of their electronic nature on the optical properties of the push-pull systems.

We report in this work the synthesis and the photophysical characterization of novel thienylpyridazine derivatives which were synthesized through Suzuki coupling of 3-bromo-6-(thiophen-2-yl)pyridazine³ with commercially available (hetero)aryl-boronic acids.

References:

1. (a) Dalton, L. R.; Sullivan, P. A.; Bale, D. H.; Chem. Rev., 2010, 110, 25. (b) Misha, A.; Fischer, M. K. R.; Bauerle, P.; Angew. Chem. Int. Ed., 2009, 48, 2479. (c) Mishra, A.; Ma, C.-Q.; Baeuerle, P.; Chem. Rev., 2009, 109, 1141. (d) Handbook of Thiophene-Based Materials: Applications in Organic electronics and Photonics; Perepichka, F., Perepichka, D. F., Ed.; Wiley: New York, 2009.
2. For some recent examples see: (a) Fernandes, S. S. M.; Castro, M. C. R.; Mesquita, I.; Andrade, L.; Mendes, A.; Raposo, M. M. M.; Dyes Pigments 2017, 136, 46. (b) Garcia-Amorós, J.; Castro, M. C. R.; Coelho, P.; Raposo, M. M. M.; Velasco, D; Chem. Commun. 2016, 52, 5132. (c) Castro, M. C. R.; Belsley, M.; Raposo, M. M. M.; Dyes Pigments 2016, 131, 333. (d) Pina, J.; Seixas de Melo J. S.; Batista, R. M. F.; Costa, S. P. G.; Raposo, M. M. M.; J. Org. Chem.2013, 78, 11389.
3. Raposo, M. M. M.; Sampaio, A. M. B. A; Kirsch, G.; J. Heterocyclic Chem. 2005, 42, 1245.

Acknowledgements: Thank are due to Fundação para a Ciência e Tecnologia (Portugal) and FEDER-COMPETE for financial support through the Centro de Química PEst-C/QUI/UI0686/2011 (F-COMP-01-0124-FEDER-022716) and a PhD grant to S. S. M. Fernandes (SFRH/BD/87786/2012). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased with funds from FCT and FEDER.