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Amino Acid-Catalyzed Neogenesis of Carbohydrates: A Plausible Ancient Transformation
Stockholm University, Faculty of Science, Department of Organic Chemistry.
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2005 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 11, no 16, 4772-4784 p.Article in journal (Refereed) Published
Abstract [en]

Hexose sugars play a fundamental role in vital biochemical processes and their biosynthesis is achieved through enzyme-catalyzed pathways. Herein we disclose the ability of amino acids to catalyze the asymmetric neogenesis of carbohydrates by sequential cross-aldol reactions. The amino acids mediate the asymmetric de novo synthesis of natural L- and D-hexoses and their analogues with excellent stereoselectivity in organic solvents. In some cases, the four new stereocenters are assembled with almost absolute stereocontrol. The unique feature of these results is that, when an amino acid is employed as the catalyst, a single reaction sequence can convert a protected glycol aldehyde into a hexose in one step. For example, proline and its derivatives catalyze the asymmetric neogenesis of allose with >99 % ee in one chemical manipulation. Furthermore, all amino acids tested catalyzed the asymmetric formation of natural sugars under prebiotic conditions, with alanine being the smallest catalyst. The inherent simplicity of this catalytic process suggests that a catalytic prebiotic “gluconeogenesis” may occur, in which amino acids transfer their stereochemical information to sugars. In addition, the amino acid catalyzed stereoselective sequential cross-aldol reactions were performed as a two-step procedure with different aldehydes as acceptors and nucleophiles. The employment of two different amino acids as catalysts for the iterative direct aldol reactions enabled the asymmetric synthesis of deoxysugars with >99 % ee. In addition, the direct amino acid catalyzed C2+C2+C2 methodology is a new entry for the short, highly enantioselective de novo synthesis of carbohydrate derivatives, isotope-labeled sugars, and polyketide natural products. The one-pot asymmetric de novo syntheses of deoxy and polyketide carbohydrates involved a novel dynamic kinetic asymmetric transformation (DYKAT) mediated by an amino acid.

Place, publisher, year, edition, pages
2005. Vol. 11, no 16, 4772-4784 p.
Keyword [en]
aldol reaction, amino acids, asymmetric synthesis, carbohydrates, polyketides
National Category
Other Basic Medicine
URN: urn:nbn:se:su:diva-23702DOI: 10.1002/chem.200500139OAI: diva2:194029
Available from: 2005-04-07 Created: 2005-04-07 Last updated: 2010-10-29Bibliographically approved
In thesis
1. Direct Amino Acid-Catalyzed Enantioselective α-Oxidation Reactions and Asymmetric de novo Synthesis of Carbohydrates
Open this publication in new window or tab >>Direct Amino Acid-Catalyzed Enantioselective α-Oxidation Reactions and Asymmetric de novo Synthesis of Carbohydrates
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The ability of amino acids to form nucleophilic enamines with aldehydes and ketones has been used in the development of asymmetric α-oxidation reactions with electrophilic oxidizing agents. Singlet molecular oxygen has for the first time been asymmetrically incorporated into aldehydes and ketones, and the products were isolated as their corresponding diols in good yields and ee’s. Organocatalytic α-oxidations of cyclic ketones with iodosobenzene and N-sulfonyloxaziridine were also possible and furnished after reduction the product diols in generally low yields and in low to good ee’s. Amino acids have also been shown to catalyze the formation of carbohydrates by sequential aldol reactions. For example, proline and hydroxy proline mediate a highly selective trimerisation of α-benzyloxyacetaldehyde into allose, which was obtained in >99 % ee. Non linear effect studies of this reaction revealed the largest permanent nonlinear effect observed in a proline-catalyzed reaction to date. Moreover, polyketides were also assembled in a similar fashion by an amino acid-catalyzed one-pot reaction, and was successful for the trimerisation of propionaldehyde, however the sequential cross aldol reactions suffered from lower selectivities. This problem was overcome by the development of a two-step synthesis that enabled the formation of a range of polyketides with excellent selectivities from a variety of aldehydes. The method furnishes the polyketides via the shortest route reported and in comparable product yields to most multi-step synthesis. All polyketides were isolated as single diastereomers with >99 % ee. Based on the observed amino acid-catalysis, amino acids are thought to have taken part in the prebiotic formation of tetroses and hexoses.

Place, publisher, year, edition, pages
Stockholm: Institutionen för organisk kemi, 2005
Organo catalysis
National Category
Organic Chemistry
urn:nbn:se:su:diva-449 (URN)91-7155-035-6 (ISBN)
Public defence
2005-04-28, sal G, Arrheniuslaboratorierna, Svante Arrhenius väg 14-18, Stockholm, 10:00
Available from: 2005-04-07 Created: 2005-04-07Bibliographically approved

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Córdova, Armando
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