Traceless chiral coupling reagent. A new concept for synthesis of optically active products from racemic carboxylic acids.

Beata Kolesińska 1Katarzyna Kasperowicz-Frankowska Justyna Frączyk 1Zbigniew J. Kamiński 1

1. Technical University of Łódź, Institute of Organic Chemistry (PŁ), Żeromskiego 116, Łódź 90-924, Poland

Abstract

The advances in stereoselective bioanalysis led to a new awareness of the importance of stereoselective pharmacodynamics and pharmacokinetics, enabling the differentiation of the relative contributions of enantiomers to overall drug action. This results in formal obligation to recognize the occurrence of chirality in new drugs, attempt to separate the stereoisomers, assess the contribution of the various stereoisomers to the activity of interest and make a rational selection of the stereoisomeric form that is proposed for marketing. In order to facilitate this studies in case of syntheses involving condensation of chiral carboxylic acid we developed the concept of a traceless chiral coupling reagent useful for enantioselective synthesis of optically active products (also peptides) from racemic carboxylic acids (amino acids). According to the concept coupling reagents consists of two fragments with chiral auxiliary responsible for enantioselectivity expelled just during activation of carboxylic group. The reagent were prepared by the treatment of chiral ammonium tetrafluoroborate (1) with 2-chloro-4,6-dimethoxy-1,3,5-triazine (2) in the presence of sodium bicarbonate yielding stable N-(4,6-dimethoxy-1,3,5-triazin-2-yl)ammonium tetrafluoroborate (3) in high yield [1a]. Chiral coupling reagents 3 were found stable at room temperature and in a broad range of solvents yielded in high yield acylated products (amides, esters and peptides) [1b] with fully predictable configuration and ee (dr) ranging from 95/5 to 60/40 under reaction conditions identical as optimized for its achiral equivalent.

Acknowledgement: This work was supported by MSHE Grants 6/PMPP/U/30-09.08/E-370/2009 and N N204 326737.

Literature:

[1] (a) B. Kolesińska, Z.J. Kamiński, Org. Lett., 11 (3), 765-768 (2009). (b) B. Kolesińska, K. Kasperowicz, M. Sochacki, A. Mazur, S. Jankowski, Z.J. Kamiński. Tetrahedron Lett. 51, 20–22 (2010).

Legal notice
  • Legal notice:

    Copyright (c) Pielaszek Research, all rights reserved.
    The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
    In every case, proper references including Author(s) name(s) and URL of this webpage: http://science24.com/paper/23120 must be provided.

 

Related papers
  1. Preliminary studies on application of library of artificial receptors for differentiation of metabolites in urine of healthy and cancer mice
  2. Synthesis of chiral triazine coupling reagents based on esters of N-alkylproline and their application in the enantioselective incorporation D or L amino acid residue directly from racemic substrate
  3. 1,3-Oxazolidin-5-ones as chiral components in the synthesis of traceless enantioselective reagents
  4. Attempts to application of libraries of N-lipidated amino acids and peptides immobilized   on cellulose as a stereosectors
  5. An Approach for Application of Synthetic Peptides as Markers of Atherosclerotic Diseases
  6. Synthesis and Antimicrobial Activity of P-Tria- zinylphosphonium Salts
  7. An approach towards efficient peptide synthesis in aqueous solution
  8. Synthesis and application of library of artificial receptors immobilized on cellulose support
  9. Design and synthesis of libraries of artificial enzymes
  10. Sulfonates of N-Triazinylammonium Salts as Highly Efficient and Environmentally Friendly Triazine-Based Coupling Reagents
  11. Rate of Binding of Host Molecules to Artificial Receptors Formed by Self-Organisation of Lipidated Oligopeptides
  12. Synthesis of Building Blocks Containing Glycosyl Moieties by Using Triazinylammonium Sulfonates
  13. Transformation of Tertiary Amines into N-Triazinylated Analogues by Treatment with Chloro-1,3,5-Triazines
  14. The New Analogues of Nitrogen Mustard With One, Two or Three 2-Chloroethylamino Fragments. Reactions with Nucleophiles
  15. Synthesis and Screening of the Library of the Supramolecular Structures Formed by N-Lipidated Oligopeptides for Selection of Host Active as Artificial Esterase
  16. AN APPLICATION OF THE ARRAY OF LIPIDATED OLIGOPEPTIDES RESEMBLING ARTIFICIAL RECEPTORS FOR MOLECULAR RECOGNITION. THE STUDIES ON THE LIPOPHLILICITY OF SOME PIPERAZINES
  17. SYNTHESIS AND SEROLOGICAL INTERACTIONS OF H.PYLORI UREASE FRAGMENT 321-339 IMMOBILIZED ON THE CELLULOSE SUPPORT
  18. AN APPLICATION OF CHIRAL COUPLING REAGENTS FOR ENANTIOSELECTIVE ACTIVATION OF RACEMIC N-BENZOYL- 2-HYDROXYMETHYL-2-AMINO ACIDS
  19. THE NEW WATER SOLUBLE SALTS, PRONE TO SPONTANEOUS DECOMPOSITION WITH FORMATION OF 2-CHLOROETHYLAMINO MOIETY (NITROGEN MUSTARD DERIVATIVES)

Presentation: Oral at VII Multidyscyplinarna Konferencja Nauki o Leku, by Beata Kolesińska
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-19 18:23
Revised:   2010-03-20 08:49
Google
 
Web science24.com
© 1998-2022 pielaszek research, all rights reserved Powered by the Conference Engine