Chemistry of Natural Products and Bioactive Synthetics

Natural Products Synthesis

The Natural Products Synthesis Group (SIPN), one of the oldest in the IPNA-CSIC, seeks to  develop new synthetic methodologies based on the use of light, for selective modification of biomolecules to obtain products of interest.

The Natural Products Synthesis Group profile page on Digital.CSIC.

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Síntesis de productos naturales
Presentation

The research lines of our group have evolved to focus on the field of synthetic methodology, especially radical chemistry. Thus, the reactions of β-fragmentation (β-FRA) and intramolecular transfer of hydrogen (TIH) promoted by alcoxyl or amidyl radicals, in the presence of hypervalent iodine reagents, such as (diacetoxyiodine)benzene (DIB) or iodine-sylbenzene, and iodine with excellent results, have been extensively studied, fine-tuning a methodology, known as the Suarez Reaction, which internationally characterises our group. This protocol involves the regioselective functionalization of C-H links in a highly efficient and sustainable manner.

Among the most interesting novel contributions of the Suarez conditions are their application to carbohydrates and steroids to obtain a wide battery of glycomimetics and chiral synthetic forms, which are difficult to obtain by other methods.

Currently, we have extended this methodology to other types of accessible natural enantiopure products. Additionally, other processes for the chemoselective modification of organic molecules are being studied under diverse reaction conditions, such as in reducing medium, photochemicals or other applications of the various redox systems of halogens.

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Descarboxilacion_oxidativa_fotorredox_Ciclodextrinas_PORTADA

Oxidative and photoredox decarboxylation of cyclodextrins

This line of research focuses on the study of the radical β-fragmentation reaction induced by light to promote the decarboxylation of mono- and di-carboxylic acids in cyclic polysaccharide systems, such as cyclodextrins.

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Intramolecular Hydrogen Atom Transfer Reactions (HAT) promoted by photochemical excited carbonyls

This research line started 10 years ago and is focused on the study of HAT reactions promoted by photochemically excited carbonyls.

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Figura1

Intramolecular Transfer Processes 1,8 in Complex Carbohydrate Systems

Intramolecular hydrogen transfer (IHT) radical reactions involving six- and seven-member transition states are very common, while those via seven-member transition states are scarce. Recently, our group has pioneered an unusual 1,8-TIH process in (1→4)-O-disaccharides systems promoted by the 6-O...

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Alkoxyl Radical Fragmentation Reaction

The alkoxyl radical fragmentation (ARF) reaction1 is a research line that has been developed by this laboratory. In previous studies2 by our research group, we have described that starting from carbohydrates (a) by β-fragmentation of alkoxyl radicals (FRA), generated by...

GeoBiomimetic Applications of the Iodine Reactivity in the Field of the Organic Synthesis

In this research line, our efforts are focused on a better understanding on the fascinating redox iodine systems in different environments. A relevant observed feature of this redox system has been the dynamicity within the iodine transient species interconversions driving us to the concept of...

Transferencia de átomos de Hidrógeno promovida por excitación fotoquímica de 1,2-dicetonas

Año:2019
Director del trabajo:

Dra. Elisa Isabel de León Alonso y Prof. Ernesto Suárez López

Estudiante:

Dimitri Alexander Álvarez Dorta

Tipo:Tesis doctoral

Fragmentación radicalaria de alcoholes anoméricos de carbohidratos: Síntesis de Heterociclos Polihidroxilados y Evaluación de su Actividad Biológica

Año:2019
Director del trabajo:

Dra. Concepción González Martín y Prof. Ernesto Suárez López

Estudiante:

Andrés González Santana

Tipo:Tesis doctoral

Síntesis de Compuestos Organofosforados Altamente Funcionalizados, mediante Fragmentación de Radicales Alcoxilo Anóméricos de Carbohidratos. Aplicaciones Sintéticas

Año:2019
Director del trabajo:

Dra. María del Sol Rodríguez Morales y Prof. Ernesto Suárez López

Estudiante:

Daniel Hernández Guerra

Tipo:Tesis doctoral

Desarrollo de nuevas metodologías para la síntesis de azepanos

Año:2019
Director del trabajo:

Dra. Concepción González Martín y Prof. Cosme García Francisco

Estudiante:

Dionisio José Rodríguez Sosa

Tipo:Máster y TFG

Desarrollo de Nuevas Metodologías para la síntesis de inhibidores de glicosidasas y glicosiltransferasas y aplicación de la fotociclación de 1,2-dicetonas en el diseño de nuevos derivados polihidroxilados

Año:2019
Director del trabajo:

Dr. Antonio J. Herrera González y Prof. Ernesto Suárez López

Estudiante:

María Eugenia Rondón Rivas

Tipo:Tesis doctoral

Reacciones de Transferencia de Hidrógeno en Sistemas de Furanosas

Año:2019
Director del trabajo:

Dra. Ángeles Martín Hernández y Dra. Inés Pérez Martín

Estudiante:

Adrián Semidán Montes Alberto

Tipo:Máster y TFG
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Gobierno de Canarias

Radicales Libres en la Síntesis de Nuevos Glicomiméticos con Potencial Actividad Terapeútica

Investigador principal:

Mª Ángeles Martín Hernández

Estado:

En Ejecución

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caja canarias

Preparación de Nuevas Estructuras de Ciclodextrinas para el Transporte de Fármacos

Investigador principal:

Mª Ángeles Martín Hernández

Estado:

Finalizado

Proyecto de investigación

Aplicaciones Sintéticas de los Procesos de Transferencia Intramolecular de Hidrógeno en Sistemas de Carbohidratos. Obtención de Nuevos Sintones Quirales

Investigador principal:

Mª Ángeles Martín Hernández

Estado:

Finalizado

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Gobierno de Canarias

Diseño de compuestos enantioméricamente puros utilizando nuevas metodologias basadas en C-, N-y O-radicales. Aplicación a la síntesis de sustancias con actividad biológica

Investigador principal:

Concepción González Martín

Estado:

Finalizado

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Gobierno de Canarias

Reacciones de Transferencia Intramolecular de Hidrógeno sobre Carbohidratos. Nuevas Metodologías para la Síntesis de Compuestos Potencialmente Bioactivos

Investigador principal:

Mª Ángeles Martín Hernández

Estado:

Finalizado

News/Blog

Selected Publications

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Reductive Radical Cascades

Reductive Radical Cascades Triggered by Alkoxyl Radicals in the β-Cyclodextrin Framework

The generation and fate of 2,3,6-icosa-O-methyl-β-cyclomaltoheptaos-6-O-yl radical under reductive conditions is described. Two radical cascade reactions are involved: the main one is triggered by a 1,8-HAT of the hydrogen at 5C. The radical can reach the anomeric hydrogen at 1C three sugar units ahead using a six-step sequence. The different hydrogen donor ability of the group 14 hydrides permits one to selectively stop the cascade at 5C, 2C, and 4C to obtain β-CD with a β-l-Idop unit, acyclic hepta-, and hexa-saccharide structures, respectively.

León, Elisa I.; Martín, Ángeles; Pérez-Martín, Inés; Suárez, Ernesto 

Organic Letters 20(11): 3385-3389 (2018)
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Chemoselective Intramolecular Functionalization

Chemoselective Intramolecular Functionalization of Methyl Groups in Nonconstrained Molecules Promoted by N-Iodosulfonamides

Mechanistic evidence observed in Hofmann–Löffler–Freytag-type reactions has been crucial to achieve the chemoselective functionalization of methyl groups under mild conditions. Radical-mediated methyl iodination and subsequent oxidative deiodination are the key steps in this functionalization, where iodine chemistry has a pivotal role on the formation of the C–N bond. The concepts of single hydrogen atom transfer (SHAT) and multiple hydrogen atom transfer (MHAT) are introduced to describe the observed chemoselectivity.

Paz, Nieves R.; Rodríguez Sosa, Dionisio; Valdés, Haydée; Marticorena, Ricardo; Melián, Daniel; Copano, Belén; González Martín, Concepción C.; Herrera, Antonio J.

Organic Letters 17(10): 2370-2373 (2015)
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Easy Access to Modified Cyclodextrins

Easy access to modified cyclodextrins by an intramolecular radical approach

A simple method to modify the primary face of cyclodextrins (CDs) is described. The 6I‐O‐yl radical of α‐, β‐, and γ‐CDs regioselectively abstracts the H5II, located in the adjacent D‐glucose unit, by an intramolecular 1,8‐hydrogen‐atom‐transfer reaction through a geometrically restricted nine‐membered transition state to give a stable 1,3,5‐trioxocane ring. The reaction has been extended to the 1,4‐diols of α‐ and β‐CD to give the corresponding bis(trioxocane)s. The C2‐symmetric bis(trioxocane) corresponding to the α‐CD is a stable crystalline solid whose structure was confirmed by X‐ray diffraction analysis. The calculated geometric parameters confirm that the primary face is severely distorted toward a narrower elliptical shape for this rim.

Álvarez-Dorta, Dimitri; León, Elisa I.; Kennedy, Alan R.; Martín, Ángeles; Pérez-Martín, Inés; Suárez, Ernesto

Angewandte Chemie International Edition 54(12): 3674-3678 (2015)
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Fragmentation of Carbohydrate Anomeric

Fragmentation of carbohydrate anomeric alkoxyl radicals: Synthesis of chiral polyhydroxylated β-iodo- and alkenylorganophosphorus(V) compounds

A direct approach to β‐iodophosphonates and β‐iodophosphine oxides from 2,3‐dideoxy‐3‐phosphoryl carbohydrate derivatives has been achieved by using the anomeric alkoxyl radical 1,2‐fragmentation protocol. The reaction has been conducted on carbohydrate derivatives under mild conditions with (diacetoxyiodo)benzene and molecular iodine. Subsequent dehydroiodination afforded the corresponding vinylphosphonates and vinylphosphine oxides.

Hernández-Guerra, Daniel; Rodríguez Morales, María S.; Suárez, Ernesto 

European Journal of Organic Chemistry 2014(23): 5033-5055 (2014)
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Sequential Norrish type II

Sequential Norrish type II photoelimination and intramolecular aldol cyclization of α-diketones: Synthesis of polyhydroxylated cyclopentitols by ring contraction of hexopyranose carbohydrate derivatives

The excitation of the innermost carbonyl of nono‐2,3‐diulose derivatives by irradiation with visible‐light initiates a sequential Norrish type II photoelimination and aldol cyclization process that finally gives polyfunctionalized cyclopentitols. The rearrangement has been confirmed by the isolation of stable acyclic photoenol intermediates that can be independently cyclized by a thermal 5‐(enolexo)‐exo‐trig uncatalyzed aldol reaction with high diastereoselectivity. In this last step, the large deuterium kinetic isotope effect found for the 1,5‐hydrogen atom transfer seems to indicate that the aldol reaction runs through a concerted pericyclic mechanism. Owing to the ready availability of pyranose sugars of various configurations, this protocol has been used to study the influence of pyranose ring‐substituents on the diastereoselectivity of the aldol cyclization reaction. In contrast with other pyranose ring contraction methodologies no transition‐metal reagents are needed and the sequential rearrangement occurs simply by using visible light and moderate heating (0 to 60 °C).

Álvarez‐Dorta, Dimitri; León, Elisa I.; Kennedy, Alan R.; Martín, Ángeles; Pérez-Martín, Inés; Riesco-Fagundo, Concepción; Suárez, Ernesto 

Chemistry - A European Journal 19(31): 10312-10333 (2013)
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Synthesis of Chiral β-Iodo

Synthesis of Chiral β-Iodo- and Vinylorganophosphorus(V) Compounds by Fragmentation of Carbohydrate Anomeric Alkoxyl Radicals

A new general methodology for the synthesis of chiral vinylphosphonate and vinylphosphine oxide carbohydrate derivatives has been developed using the anomeric alkoxyl radical fragmentation reaction as the key step. The synthetic sequence proceeded via β-iodophosphonate and β-iodophosphine oxide intermediates, which may be interesting synthons for the introduction of phosphorus into organic molecules. These vinylphosphonates could be easily transformed into 2-methylene-1-phosphapentofuranoses (3-methylene-1,2-oxaphospholanes) and β-aminophosphonates, isosteres of biologically active α-methylene-γ-lactones and β-amino acids, respectively.

Hernández-Guerra, Daniel; Rodríguez Morales, María S.; Suárez, Ernesto

Organic Letters 15(2): 250-253 (2013)

Other research groups

Química de Productos Naturales y Sintéticos Bioactivos

Chemistry of Natural Products and Bioactive Synthetics