Imine derivatives are an important class of compounds due their biological and optical properties making them suitable for several applications such as chemosensor, photochromic, and others.^1,2 In recent years the search for new colorimetric chemosensors for anions has been of great interest because of the role that ions play in chemical and biological processes.³  In this context and as part of an on-going research to develop efficient heterocyclic systems for photochromic and chemosensor applications⁴ we report in this communication the synthesis, the photophysical characterization and the chemosensor ability of pyrrolidene heterocyclic imines functionalized with aryl or naphthyl moieties.

In this work, we describe the synthesis of novel triazolylmethyl-pyrrolo[3,4-b]pyridin-5-ones by a sequence: Ugi-3CR / aza Diels-Alder / Click. There are several reports about pyrrolo[3,4-b]pyridin-5-ones related to various type of biological activity.We reported two methodologies for synthesizing series of novel pyrrolo[3,4-b]pyridine-5-ones using Ugi reactions combined with further condensation processes. In the first, a series of tetrahydroisoquinolin-pyrrolopyridinones was prepared by a sequence: Ugi-3CR / aza Diels-Alder / Pummerer. In the second, aza-analogs of the natural alkaloid (±)-nuevamine were prepared by a sequence: Ugi-3CR / aza Diels-Alder / Pictet-Spengler. By using Ugi-3CR/ Aza Diels-Alder cycloaddition for the synthesis of propargyl-pyrrolopyridine intermediates with the previously-well established conditions combining propargyl amine, aldehydes, α-isocyanoamides and maleic anhydride in toluene with Sc(OTf)₃ in MW followed by CuAAC sequence for the synthesis of triazolyl products.

A series of nine novel 3-acetamide-azepino[4,5-b]indol-4-ones and nine novel 3-tetrazolylmethyl-azepino[4,5-b]indol-4-ones were synthesized by Ugi-type / free radical mediated cyclization in moderate to good yields (52-90%) and (40-83%) respectively. Several stepwise methodologies toward compounds having the azepino[4,5-b]indol-4-one core have been reported in which the last step was the construction of the azepine ring e.g. via: (i) S_EAr, (ii) Pd-catalyzed alkyne arylations, (iii) lactamizations, (iv) photocyclizations, and (v) free radical mediated. Azepino[4,5-b]indol-4-one is the core of various natural bioactive products such as the malassezindoles.  The main hypothesis in this work was that the 3-tetrazolylmethyl-azepino[4,5-b]indol-4-ones and the 3-acetamide-azepino[4,5-b]indol-4-ones may show binding affinity on the 5-Ht₆R and hence may be candidates to further assays in vitro as 5-Ht₆R antagonists. Interestingly, a lead binding value was exhibited by one of our 3-acetamide-azepino[4,5-b]indol-4-ones (Ki = 211 nM).

Nowadays, the high prevalence and incidence of neurodegenerative diseases, such as Parkinson, Alzheimer or amyotrophic lateral sclerosis diseases makes an important field to search for novel molecules to access different customized treatment. In this context, monoaminooxidase (MAO) inhibitors have been used for this purpose in the initial stage of Parkinson’s disease.

Coumarins have demonstrated to provide a wide range of biological activities including MAO inhibitor capability. Additionally, this kind of compounds shows fluorescence properties improving its detection at physiological environments. However, these compounds often suffer from poor solubility. With the aim of solving this drawback, following the strategy carrier pro-drug, coumarin attachment to a carbohydrate residue allowed us to improve this disadvantage.

Herein, we report the synthesis and characterization of coumarin glycosides by reaction of a glycosyl halide with coumarin derivatives. The reaction has been optimised to achieve good selectivities and yields. For this purpose, mechanistic considerations based on DFT calculations have been also performed. Finally, the determination of the enzymatic parameters has shown that the carbohydrate-coumarin derivative is an efficient drug-releasing system.We thank the AECID (Projects A/023577/09 and A/040322/10) and the ‘Junta de Andalucía’ (FQM 142 and Project P09-AGR-4597) for financial support.

Novel cyclohexapeptide has been synthesized by replacing the unusual amino acids (dolaphenvaline and dolaphenleuine) of dolastatin 16 with (±)-cis-exo-norbarnane and phenyl alanine amino acids. Novel cyclic hexapeptide alongwith dimers, tetramers composed of alternating L-proline subunits have been synthesized in solution phase and well characterized.

The development of efficient methods for the synthesis of heterocyclic compounds is always of great importance for chemists. In this perspective, we describe a general approach for the synthesis of functionalized heterocyclic via Ugi MCR followed by intramolecular ylide initiated Michael reaction, In this case, the reaction proceeds via in-situ generated phosphorus ylides. We especially emphasize the importance of tuning the Ugi adduct for the points of molecular diversity by designing intramolecular ylide initiated Michael reaction with chromone based Ugi adduct as Michael acceptor, 2-chloro acetic acid as acid component in Ugi reaction that helps for in-situ generation of phosphorus ylides that allows formation of a different class of heterocyclic stable ylides. The Ugi reaction with 3-formyl chromone, amine, isocyanide and 2-chloro acetic acid with equimolar quantity at classical Ugi conditions in methanol 1M under microwave irradiation for 10 min to obtain Ugi adduct which susbsequentially reacted with tripheylphosphine that generates phosphonium salt based Ugi adduct as intermediate that undergoes nucleophilic conjugate addition at 2nd position of chromone  to obtain a highly functionalized stable ylide by ring opening of chromone moiety in good to moderate yields.

A mild, efficient and eco-friendly protocol for the chemoselective protection of benzylalcohol and primary alcohols is developed in presence of ZnFe₂O₄@ZnO as the catalyst. Easy work-up, relatively short reaction times, excellent yields, low cost and reusability of the catalyst are the striking properties of this methodology, which can be considered to be one of the best and general routs for the protection of alcohols.

Thioamides are great importance in medicinal chemistry due to their biological activity. For example, against bacterial infection, anti-fungicides, herbicides and anti-ulcerative agents. Thioamide intermediates are versatile in synthesis of pharmaceutical ingredients, such as Diclofenac, Fenclofenac, Ibufenac, Naproxene and in peptide chemistry.[1] Furthermore, the thioamide derivatives can be readily converted to the corresponding carboxylic acids or thioesters. Therefore, developing of more efficient methods working under mild condition is in high demand.[2] Thioamides are traditionally prepared by thionation of the corresponding amides using phosphorus pentasulfide or the Lawesson reagent.[3] Surprisingly, the Willgerodt–Kindler reaction for thioamide synthesis has received very little attention (especially in recent years). Today, the Willgerodt–Kindler reaction can be classified as a one-pot, three-component process for the synthesis of synthetically useful (thio) amides.

In continuation of our interest to use biopolymers for organic transformations, Cu(I)@Chitosan was used as an efficient heterogeneous nano-bio catalyst for Willgerodt–Kindler reaction.[4] This catalyst can be played a considerable role in thioamide bond formation. Easy preparation and separation, mild acidity and basicity, stability and reusability of the catalyst, motivated us to explore its potential to catalyze reaction. Using ultrasound irradiation as a clean source of energy, aqueous media, ambient temperature, high yield and short reaction time are outstanding features of this work.           

References:

[1] D. Priebbenow, C. Bolm; Chem. Soc. Rev. 2013, 42, 7870-7880.

[2] S.D. Salim, S.P. Pathare, K.G. Akamanchi; Catal. Commun. 2011, 13, 78-81.

[3] T. Ozturk, E. Ertas ad O. Mert; Chem.Rev. 2010, 110, 3419-3478.

[4] R.N. Baig, R.S. Varma; Green. Chem. 2013, 15, 1839-1843.

A general four-step approach to 1,2,3,7,8,8a-hexahydropyrido[4,3-d]pyrimidin-2-ones via Staudinger/intramolecular aza-Wittig reaction of 5-acyl-4-(β-azidoalkyl)-1,2,3,4-tetrahydropyrimidin-2-ones promoted by PPh₃ was developed. Synthesis of the starting pyrimidinones included preparation of 3-azidoaldehydes by the addition of hydrazoic acid to α,β-unsaturated aldehydes, transformation of 3-azidoaldehydes into N-[(3-azido-1-tosyl)alkyl]ureas followed by the reaction with 1,3-diketone enolates and dehydration of the resulting products under acidic conditions.

We report here the straightforward synthesis of some d-block metal dimers of a Schiff base ligand obtained by condensation of 2‑tosylaminomethylaniline with  4-formyl-3-hydroxybenzoic acid (H₂L). The easy bideprotonation of both -OH and ‑HNSO₂- groups, as well as a suitable N,N,O binding domain that can simultaneously bind two metal ions through µ₂-N_sulfonamido bridges have been considered during the design step of the Schiff base ligand. All the compounds synthetised were characterised by a combination of ¹H NMR spectroscopy, infrared spectroscopy, mass spectrometry and elemental analysis. We have used 2‑D NOESY spectra of some of the compounds for structure elucidation in solution.