Carlos E. Puerto Galvis

The study of metal-free and palladium-catalysed synthesis of benzochromenes via direct C–H arylation using unactivated aryl benzyl ethers derived from essential oils as raw materials

The synthesis of 6H-benzo[c]chromenes from unactivated 2-bromo aryl benzyl ethers was studied through two approaches: (i) the transition-metal-free intramolecular dehydrohalide coupling via intramolecular homolytic aromatic substitution; and (ii) the intramolecular cyclization via direct C–H arylation catalysed by PdCl2(MeCN)2. Having developed the most efficient method, a 17-membered chromene library was prepared in good yields and in shorter reaction times starting from commercially available phenol derivatives and phenol-rich essential oils (Eugenia caryophyllys and Plectranthus amboinicus) as raw materials, proving how sustainable and eco-friendly our protocol is. Additionally, the ruggedness of the optimized reaction conditions was evaluated with N-benzylanilines, giving the respective phenanthridone as an unexpected product, while the metal-free oxidation of the obtained 6H-benzo[c]chromenes was also performed to furnish the benzocoumarins.

Ce(SO4)2-catalysed the highly diastereoselective synthesis of tetrahydroquinolines via an imino Diels Alder ABB′ type reaction and their in vivo toxicity and imaging in zebrafish embryos

An efficient and practical approach has been developed for the synthesis of N-(tetrahydroquinolinyl-4) amides 3a–l in good yield with high diastereoselectivity. The strategy comprises the domino type ABB′ imino Diels Alder reaction catalysed by a cerium(IV) salt between anilines and N-vinyl amides for the preparation of a 12-membered library of tetrahydroquinolines that were tested for their in vivo toxicity against zebrafish embryos. Upon determining their LC50 values, N-(8-methoxy-2-methyl-tetrahydroquinolinyl-4) acetamide 3k was identified as the most toxic derivative with an LC50 below 95 μM (24 mg L−1). Finally, the phenotypes induced, at concentrations below their LC50, were analyzed at 48, 72 and 96 hours post fertilization, wherein the treated embryos manifested diverse visual phenotypes, such as big yolk sacs (3b, 3h, 3j), pericaldial edemas (3a, 3i) and red blood cells in the liver region (3b, 3l), in comparison to the morphology of the control embryos, the phenotypes could be associated with specific biological targets.

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest.

Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4‐methylquinoline, 4‐nitroquinoline‐1‐oxide (4‐NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4‐methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C‐5 to C‐8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C‐2: phenyl and 3,4‐methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C‐2 substitution with α‐, β‐, or γ‐pyridinyl groups removed 4‐methylquinoline genotoxicity. On the other hand, 4‐NQO derivatives whose genotoxic mechanism involves reduction of the C‐4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C‐2 of 4‐NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure–genotoxicity relationships and bioassay‐guided quinoline synthesis.

Novel Approaches in the Synthesis of Natural and Synthetic Fused Aza-Polycycles Toward the Development of New Bioactive Compounds

Abstract The purpose of this chapter is to review and discuss the literature that has covered the most recent and highly impact researches related with the total synthesis of alkaloids and synthetic products classified as aza-polycycles. After a general introduction, our chapter will be devoted to the recent aspects developed for the stereoselective synthesis of three main aza-polycycles: First, we will refer to the novel synthetic strategies for the preparation of selected pyrrolo[2,1-a]isoquinoline alkaloids and their synthetic derivatives that have included the pharmacophores of known bioactive natural products (nuevamine, jantimine, crispine, and cryptaustoline). In the second place, our interest will focus on methods developed to control the stereochemistry of the C-1 center in the synthesis of 1-phenethyl-1,2,3,4-tetrahydroisoquinoline alkaloids, mainly those ones isolated from Dysoxylum lenticellare: (+)-dysoxyline, (+)-colchiethanamine, (+)-colchiethine, and (+)-homolaudanosine. Then, we will describe the current protocols for the synthesis of aporphine and homoaporphine alkaloids, highlighting and putting in perspective the role of 1-phenethyltetrahydroisoquinolines in the biosynthesis of homoaporphines and how this approach could be taken into account in the future development of strategies for the preparation of analogues to these alkaloids. In the final section, the chemistry of β-carbolines, a group of naturally occurring indole alkaloids that are prevalent in Harmala species but also exist in several marine tunicates, will be analyzed in terms of the methods developed for the total synthesis of these structures, including complete saturated and unsaturated compounds containing one or more chiral center. Additionally, challenging synthetic derivatives that have shown biomedical applications will also be incorporated. We have chosen these aza-polycycles as the main topic for this chapter due to their widely known biological activities and the pharmacological potential of the new derivatives to be discovered, which make them attractive targets for the development of novel approaches for their total synthesis that here we discuss. Besides the synthetic aspects and to increase the practical usefulness of our chapter, in each section we have also included a short, but comprehensive, summary of the diverse biological activities reported and studied for these natural structures in the 2010–2015 period.

Coumarin-Based Molecules as Suitable Models for Developing New Neuroprotective Agents Through Structural Modification

The recent developments in the use of natural coumarin products and synthetic coumarin-based molecules as therapeutic agents for Alzheimer disease (AD) and Parkinson disease (PD) as well as the current methods for their synthesis and isolation are reviewed. Classic and modern syntheses of coumarin derivatives are discussed providing novel reaction conditions for Pechmann synthesis and Perkin and Knoevenagel condensations. Novel synthetic routes to accessing coumarins with diverse kinds of substituents from intermolecular or intramolecular reactions are classified and discussed. Lipinskis parameters and in silico study are also briefly mentioned and applied to some coumarins active against acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase (MAO). This chapter focuses on medicinal chemistry research with natural and synthetic coumarin molecules as cholinesterase inhibitors and/or MAO inhibitors and also as antioxidant agents. Carefully selected examples are discussed to underline the progress made in the development of natural and synthetic coumarins for potential therapeutic applications in AD and PD.

Simple Preparation of New Potential Bioactive Nitrogen-Containing Molecules and Their Spectroscopy Analysis

The impact of research on the small molecules chemistry is difficult to quantify and currently, it is still one of the most active areas of organic chemistry, medicinal chemistry and lately chemical biology. In recent years, a lot of interest has been shown in the preparation of nitrogen-containing compounds due to their numerous biologically significant activities. But it is the separation and purification process of the new synthetized organic molecules, the ones that take a key role in drug design and development.