Video Experimental Relacionado
Updated: Jul 12, 2026
09:30
The Synthesis of RGD-functionalized Hydrogels as a Tool for Therapeutic Applications
Published on: October 7, 2016
Síntesis total y confirmación estructural de la clorodisinosina A
Stephen Hanessian1, Juan R Del Valle, Yafeng Xue
1Department of Chemistry, Université de Montréal, C.P. 6128, Station Centre-ville, Montréal, P.Q., H3C 3J7 Canada.
Journal of the American Chemical Society
|August 10, 2006
Resumen
Los investigadores lograron la primera síntesis total enantio-controlada de la clorodisinosina A, un potente producto natural marino. Este avance permite un mayor estudio de su estructura y poderosas propiedades de inhibición de enzimas.
Área de la Ciencia:
- Síntesis de Productos Naturales.
- Química medicinal Química medicinal es el campo de la química medicinal.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La clorodisinosina A es un metabolito de las esponjas marinas perteneciente a la familia de las aeruginosinas.
- Se sabe que es un potente inhibidor de las proteasas serinas humanas clave involucradas en la coagulación de la sangre.
- La estructura precisa y la estereoquímica, en particular el nuevo residuo de aminoácidos clorados, no se habían aclarado completamente antes de este trabajo.
Objetivo del estudio:
- Para lograr la primera síntesis total enantio-controlada de la clorodisinosina A.
- Confirmar la estructura y la configuración absoluta de la clorodisinosina A, incluido el nuevo residuo de 2S,3R-3-cloroleucina.
- Para evaluar la clorodisinosina A como un inhibidor de las serina proteasas relevantes para la hemostasis.
Principales métodos:
- Desarrollo de una síntesis estereocontrolada y concisa para el fragmento 2S,3R-3-cloroleucina.
- Ejecución de la síntesis total controlada por enantio de la clorodisinosina A.
- Cocristalografía de rayos X de clorodisinosina sintética A unida a la trombina para la confirmación estructural.
Principales resultados:
- Se logró una síntesis total enantio-controlada exitosa de la clorodisinosina A.
- La estructura cocristalina de rayos X confirmó la estructura propuesta y la configuración absoluta.
- La clorodisinosina A demostró una potente inhibición contra la trombina, el factor VIIa y el factor Xa.
Conclusiones:
- La síntesis total proporciona una asignación estructural y estereoquímica definitiva de la clorodisinosina A.
- La clorodisinosina A es el inhibidor más potente conocido dentro de la familia de las aeruginosinas para las proteasas clave de la coagulación.
- Este trabajo facilita una mayor investigación sobre el potencial terapéutico de la clorodisinosina A y sus compuestos relacionados.
Más Videos Relacionados
Videos de Conceptos Relacionados
03:05Acid Strength and Molecular Structure
Binary Acids and Bases
In the absence of any leveling effect, the acid strength of binary compounds of hydrogen with nonmetals (A) increases as the H-A bond strength decreases down a group in the periodic table. For group 17, the order of increasing acidity is HF < HCl < HBr < HI. Likewise, for group 16, the order of increasing acid strength is H2O < H2S < H2Se < H2Te. Across a row in the periodic table, the acid strength of binary hydrogen compounds increases with increasing...
In the absence of any leveling effect, the acid strength of binary compounds of hydrogen with nonmetals (A) increases as the H-A bond strength decreases down a group in the periodic table. For group 17, the order of increasing acidity is HF < HCl < HBr < HI. Likewise, for group 16, the order of increasing acid strength is H2O < H2S < H2Se < H2Te. Across a row in the periodic table, the acid strength of binary hydrogen compounds increases with increasing...
01:15Carboxylic Acid Derivatives: Overview
Carboxylic acid derivatives are formed by replacing the hydroxyl group of carboxylic acids with a different functional group. The most common carboxylic acid derivatives are:
01:28Structures of Carboxylic Acid Derivatives
Structure of Carboxylic Acid Derivatives
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the unhybridized p...
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the unhybridized p...
01:07Acid Halides to Amides: Aminolysis
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
01:07Preparation of Acid Anhydrides
One of the methods for preparing symmetrical or unsymmetrical acid anhydrides involves the treatment of acid chlorides with the sodium salt of carboxylic acids. The reaction proceeds via a nucleophilic acyl substitution.
The carboxylate ion acts as a nucleophile that attacks the carbonyl carbon of the acid chloride to form a tetrahedral intermediate. Subsequently, the re-formation of the carbonyl group with the loss of the chloride ion as a leaving group leads to the formation of an acid...
The carboxylate ion acts as a nucleophile that attacks the carbonyl carbon of the acid chloride to form a tetrahedral intermediate. Subsequently, the re-formation of the carbonyl group with the loss of the chloride ion as a leaving group leads to the formation of an acid...
01:19Structure of Amines
The hybridized nitrogen atom in amines possesses a lone pair of electrons and is bound to three substituents with a bond angle of around 108°, which is less than the tetrahedral angle of 109.5°. However, the C–N–H bond angle is slightly larger at 112°, with a carbon–nitrogen bond length of 147 pm. This carbon–nitrogen bond length of of amines is longer than the carbon–oxygen bond of alcohols (143 pm) but shorter than alkanes’ carbon–carbon bond (154 pm). These aspects are illustrated in Figure...