Oscar Forero-Doria

TBAI/TBHP-catalyzed [3 + 2]cycloaddition/oxidation/aromatization cascade and online ESI-MS mechanistic studies: synthesis of pyrrolo[2,1-a]isoquinolines and indolizino[8,7-b]indoles

A facile [3 + 2]cycloaddition/oxidation/aromatization cascade reaction for the synthesis of pyrrolo[2,1-a]isoquinolines and indolizino[8,7-b]indoles has been developed. This tandem approach was accomplished by employing tert-butyl hydroperoxide (TBHP) as the environmentally benign stoichiometric oxidant, with the catalysis of non-toxic tetrabutylammonium iodide (TBAI) and isopropanol as the green solvent. Gratifyingly, this protocol is highly versatile, as the construction of polycyclics could be tailored by readily available dipolarophiles. Only a catalytic amount of TBAI was required, as the hypervalent electrophilic iodine species (IOH) can be recovered in situ by oxidation with TBHP. Furthermore, for the first time, the mechanistic aspects and the putative intermediates associated with this cascade have been intercepted and characterized by online monitoring of the reaction by using ESI-MS/MS.

Mauritia flexuosa Presents In Vitro and In Vivo Antiplatelet and Antithrombotic Activities

Fruit from the palm Mauritia flexuosa is one of the most important species in Peru, Venezuela, Brazil, Colombia, Bolivia, and Guyana. The present study aimed to investigate the antiplatelet and antithrombotic activities of oil extracted from Mauritia flexuosa. The fatty acid contents were determined by gas chromatography—mass spectrometry. Oil extract of peel of Mauritia flexuosa was extracted by soxhlet extraction. The oil extract inhibited platelet secretion and aggregation induced by ADP, collagen, and TRAP-6 by a concentration-dependent way (0.1 to 1 mg/mL) without the participation of the adenylyl cyclase pathway and diminished platelet rolling and firm adhesion under flow conditions. Furthermore, the oil extract induced a marked increase in the rolling speed of leukocytes retained on the platelet surface, reflecting a reduction of rolling and less adhesion. At the concentrations used, the oil extract significantly decreased platelet release of sP-selectin, an atherosclerotic-related inflammatory mediator. Oil extract inhibited thrombus growth at the same concentration as that of aspirin, a classical reference drug. Finally, the data presented herein also demonstrate for the first time to our knowledge the protective effect of oil extracted from Mauritia flexuosa on platelet activation and thrombosis formation.

Polymer-supported (-)-8-phenylmenthyl Auxiliary as an Effective Solidphase Chiral Inductor in the Addition of Nucleophiles to N-acyliminium Ions

AIM AND OBJECTIVE According to our interest in developing new methods for the construction of intricate molecules, a reliable polymer-supported (-)-8-phenylmenthyl chiral auxiliary for the addition of different nucleophiles to chiral-supported N-acyliminium precursors were developed. MATERIALS AND METHODS Merrifield resin was employed to anchor (-)-8-phenylmenthol, which was prepared by nitration of (-)-8-phenylmenthyl chloroacetate followed by reduction of nitro group and subsequent Merrifield resin coupling. Treatment of a suspension of polymer-supported chloroformate and piperidinone in the presence of Et3N resulted in attachment of the substrate onto the solid-support. Treatment of the resulting resin with LiEt3BH/MeOH afforded methoxypiperidine in 87% yield. Then, the addition of allyltrimethylsilane, TMSCN, 2-(trimethylsiloxy)propene and triisopropylsilyloxyfuran and others to the N-acyliminium ion derived from chiral 2- methoxypiperidine carbamate was studied. RESULTS The stereochemical outcome of the addition of nucleophiles to the supported N-acyliminium ion derived from 2-methoxypiperidine carbamate was proposed through the Si-face, affording after resin cleavage 2-substituted piperidines in 70%-84% yields and selectivities ranging from 4:1-11.1. Moreover, the key intermediates of chiral piperidines have been employed for the synthesis of simple chiral alkaloids such as (R)-pipecolic acid, (R)-pelletierine, (S)-coniine and (R,R)-myrtine. CONCLUSION The proposed supported-chiral auxiliary for asymmetric approach may be expected to result not only in efficient solid-phase syntheses of a wide range of alkaloids but also in the development of useful new solid-phase methodologies, particularly for the asymmetric additions to iminium precursors. This work describes the first example of solid-phase synthesis by using supported (-)-8-phenylmenthyl as an effective chiral inductor and would be useful for the synthesis of chiral building block libraries.

Effect of Sulfamic Acid on 1,3-Dipolar Cycloaddition Reaction: Mechanistic Studies and Synthesis of 4-Aryl-NH-1,2,3-triazoles from Nitroolefins

A facile and new metal-free 1,3-dipolar cycloaddition reaction for the synthesis of 4-aryl-NH-1,2,3-triazoles from nitroolefins and NaN3 employing NH2SO3H has been developed. Sulfamic acid proved to be an efficient additive in this transformation by inhibiting the formation of triaryl benzene. Mechanistic aspects and key intermediates associated with this transformation have also been characterized by online monitoring of the reaction using electrospray ionization tandem mass spectrometry method (ESI-MS/MS). The protocol emphasizes broad substrate scope for many functionalities, simple reaction conditions such as stability to open air, less reaction time, easy work-up, eco-friendly and with good to excellent yields.

Protective Effect of Pitao (Pitavia punctata (R. & P.) Molina) Polyphenols against the Red Blood Cells Lipoperoxidation and the In Vitro LDL Oxidation

The oxidative stress is characterized by an imbalance between the oxidizing agents and antioxidants; meanwhile, the consumption of antioxidants has been considered as an important tool in the prevention of oxidative stress and its consequences. Pitavia punctata (R. & P.) Molina is an endemic arboreal species from the Chilean Coast Range, in which a large amount of flavonoids has been described. This work focused on characterizing and evaluating, in human erythrocytes, the antioxidant capacity and membrane protection of P. punctata extracts and the in vitro protection of the oxidation of the Low Density Lipoprotein (LDL). The phytochemical screening revealed the presence of Quercetin derivatives and flavonoids, such as (-)-Epicatechin, Kaempferol, and derivatives. The methanolic extract presented an important antioxidant activity, protecting the membrane integrity of the red blood cells against the oxidative damage caused by Hypochlorous acid and inhibiting the oxidation of the LDL lipoprotein.

Perspectives of Dendrimer-based Nanoparticles in Cancer Therapy

Currently, cancer is the second most common cause of death in the United States, exceeded only by heart disease. Chemotherapy traditionally suffers from a non-specific distribution, with only a small fraction of the drug reaching the tumor, in this sense, the use of dendrimers incorporating drugs non-covalently encapsulated inside the dendrimer or covalently conjugated have proven to be effectives against different cancer cell lines. However, at present the dendrimers used as drug-carriers still do not meet the necessary characteristic to be considered as an ideal dendrimer for drug delivery; high toxicity, bio-degradability, low toxicity, biodistribution characteristics, and favorable retention with appropriate specificity and bioavailability have not been fully covered by the current available dendrimers. However, the development and study of new dendrimers drug-carriers continues to be an important tool in the cancer therapy as they can be functionalized with varied ligands to reach the tumor tissue through the different body barriers in the body with minimal loss of activity in the bloodstream, have the ability to selectively kill tumor cells without affecting the normal cells and most important with a release mechanism controlling actively. Given the continuous efforts and research in this area of interest, we presented in this review the work done with a special emphasis on the development of dendrimers as a major tool in the combination with drugs, as a potential adjunctive agent in anticancer therapy.

Inhibitory effects of Cyperus digitatus extract on human platelet function in vitro

Abstract The purpose of this research was to investigate the mechanisms of antiplatelet action of Cyperus digitatus. The antiplatelet action of C. digitatus was studied on platelet function: secretion, adhesion, aggregation, and sCD40L release. The platelet ATP secretion and aggregation were significantly inhibited by CDA (ethyl acetate extract) at 0.1 mg/ml and after the incubation of whole blood with CDA, the platelet coverage was inhibited by 96 ± 3% (p < 0.001). At the same concentration, CDA significantly decreased sCD40L levels. The mechanism of antiplatelet action of CDA could be by NF-κB inhibition and that is cAMP independent. In conclusion, C. digitatus extract may serve as a new source of antiplatelet agents for food and nutraceutical applications.