Alejandro Islas-Jácome

Synthesis of 3-tetrazolylmethyl-4H-chromen-4-ones via Ugi-azide and biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis

The synthesis of novel 3-tetrazolylmethyl-4H-chromen-4-ones via an Ugi-azide multicomponent reaction and their biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis are described. Reported yields are moderate to good and biological results show that these compounds could be considered as candidates to anti-parasitic drugs, especially against G. lamblia.

Synthesis of azepino[4,5-b]indol-4-ones via MCR/free radical cyclization and in vitro–in silico studies as 5-Ht6R ligands

A series of nine new 3-acetamide-azepino[4,5-b]indol-4-ones were synthesized in two steps: (i) multicomponent reaction (Ugi-4CR/SN2) and (ii) free radical-mediated cyclization. These compounds, along with their tetrazole-based analogs, were studied in vitro to assess their binding with the 5-hydroxytryptamine type 6 receptor (5-Ht6R). The 3-acetamide-azepino[4,5-b]indol-4-ones displayed moderate affinity, whereas the 3-tetrazolylmethyl-azepino[4,5-b]indol-4-ones affinity values are lower. However, one of the 3-acetamide-azepino[4,5-b]indol-4-ones exhibited a hit value of Ki (211.2nM) to the 5-Ht6R. Minimal-energy structures of one cis-amide and its tetrazole-based analog (calculated by means of the Density Functional Theory) were analyzed to assess some interesting bioisosterism aspects. Interactions and binding energies between all products and the 5-Ht6R were calculated through in silico molecular couplings. Finally, a QSAR model was proposed using the results of the in vitro assays.

Synthesis of vanillin via a catalytically active Cu(II)-metal organic polyhedron

Crystalline Cu(II)-MOP 1 was employed for the first time in the catalytic conversion of trans-ferulic acid to vanillin. The generation of uncoordinated Cu(II) metal sites within MOP 1 by activation as well as sonication, revealed its catalytic potential that afforded a reaction yield of 60%. Complementary cyclic voltammetry experiments (CVs) demonstrated the formation of the complex Cu–H2O2, which supported the reaction mechanism proposed here.

In Vitro Studies of Chromone-Tetrazoles against Pathogenic Protozoa, Bacteria, and Fungi

In vitro studies to fourteen previously synthesized chromone-tetrazoles and four novel fluorine-containing analogs were conducted against pathogenic protozoan (Entamoeba histolytica), pathogenic bacteria (Pseudomonas aeruginosa, and Staphylococcus aureus), and human fungal pathogens (Sporothrix schenckii, Candida albicans, and Candida tropicalis), which have become in a serious health problem, mainly in tropical countries.

Synthesis of 2-julolidin-imidazo[1,2-a]pyridines via Groebke–Blackburn–Bienaymé reaction and studies of optical properties

A series of sixteen new 2-julolidin-imidazo[1,2-a]pyridine bound-type bis-heterocycles were synthesized in good to excellent yields (61–98%) via an MW-assisted Groebke–Blackburn–Bienayme (GBB) reaction. Then, experimental studies were conducted to determine the luminescence properties of these compounds. Various high quantum yields were found. In fact, one product exhibited a quantum yield (86.6%) comparable to that of the reference compound rhodamine (94.8%). Finally, further computational studies were performed by means of TD-DFT to calculate their HOMO–LUMO distributions and theoretical absorption spectra. A good agreement between the experimental and computational results was obtained, which provides a rationalized explanation for the observed structure/property relationships.

Synthesis of benzo-fused spiropiperidines through a regioselective free radical-mediated cyclization as key step: a suitable alternative towards the lead σ-1 receptor ligand L-687384

Abstract The synthesis of four novel benzo-fused spiropiperidines and the lead σ-1 receptor ligand L-687384 through a xanthate-mediated free radical spirocyclization as key step is described. Furthermore, the key free radical-based cyclization was computationally studied by means of the density functional theory approach at the UB3LYP/6-311+G(d) level to understand the regioselectivity because there are three possible closure pathways and only the benzo-fused spiropiperidines (ipso products) were experimentally found.Graphical abstract

Synthesis of 1′-tetrazolylmethyl-spiro[pyrrolidine-3,3′-oxindoles] via two coupled one-pot processes Ugi-azide/Pictet–Spengler and oxidative spiro-rearrangement

Six novel tris-heterocycles 1′-tetrazolylmethyl-spiro[pyrrolidine-3,3′-oxindoles] were synthesized in 39–82% yields in two experimental steps: (i) a one-pot Ugi-azide/Pictet–Spengler process coupled to (ii) a one-pot oxidative spiro-rearrangement. The synthesized polyheterocycles could be used for further in vitro studies because they contain moieties present in various anticancer bioactive molecules and drugs.

Synthesis of Polyheterocyclic Pyrrolo[3,4-b]pyridin-5-ones via a One-Pot (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/SN2) Process. A Suitable Alternative towards Novel Aza-Analogues of Falipamil

We describe the one-pot synthesis of twenty polyheterocyclic pyrrolo[3,4-b]pyridin-5-ones via a cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization) in 20 to 95% overall yields, as well as four pharmacologically promising analogues via an improved cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/SN2): two piperazine-linked pyrrolo[3,4-b]pyridin-5-ones in 33 and 34%, and a couple of Falipamil aza-analogues in 30 and 35% overall yields. It is worth highlighting the good substrate scope found, because final products are furnished with alkyl, aryl, and heterocyclic substituents. The use of chain-ring tautomerizable isocyanides (as key reagents for the Ugi-type three component reaction) allowed for a rapid and efficient assembly of the polysubstituted oxindoles, which were used in situ toward the complex products, conferring features like robustness, sustainability, and the one-pot approach to this synthetic methodology.

Synthesis of New 5-Aryl-benzo[f][1,7]naphthyridines via a Cascade Process (Ugi-3CR/Intramolecular Aza-Diels-Alder Cycloaddition)/Aromatization

A series of eight new 5-aryl-benzo[f][1,7]naphthyridines were synthesized in 17 to 64% overall yields via an improved MW-assisted cascade-like one pot process (Ugi–three component reaction/intramolecular aza-Diels-Alder cycloaddition) coupled to an aromatization process from tri-functional dienophile-containing ester-anilines, substituted benzaldehydes and the chain-ring tautomerizable 2-isocyano-1-morpholino-3-phenylpropan-1-one as starting reagents, under mild conditions. The doubly activated dienophile and the aza-diene functionalities of the eight new Ugi-adducts were exploited to perform an in situ aza-Diels-Alder cycloaddition/aromatization (dehydration/oxidation) process, toward the complex polysubstituted 5-aryl-polyheterocycles, which could be taken as starting point for further SAR studies because the benzo[f][1,7]naphthyridine is the core of various bioactive products. It is relevant to emphasize that the synthesis or isolation of benzo[f][1,7]naphthyridines containing a substituted aromatic ring in the C-5 position, has not been published before.

Synthesis of spiro-cyclohexendienone-gamma-lactams via free-radicals and study of thermal regioselective spirocyclization

The spiro-regioisomers 1a and 1b were synthesized from the xanthate-type precursor 2 via a free-radical mediated spirocyclization in different proportions depending on the reaction temperature, from 40:1 at -45 °C to 5:1 at 150 °C. The maximum proportion relationship value was 2:1 at 110-125 °C. We hypothesize that those proportion values are due to inherent stability of the involved free radicals. In the case of the product 1a, the intermediate is a very thermodynamically stable double allyl radical. In the case of the product 1b, the intermediate is an a,b,g,d-unsaturated carbonyl radical. The products 1a-b were fully characterized by 1H and 13C NMR, FT-IR, HRMS, and even by X-ray analysis because adequate crystals were obtained for both products, (1a, CCDC: 1050852) and (1b, CCDC: 1050853) respectively.