1,3-Oxazolidin-5-ones as chiral components in the synthesis of traceless enantioselective reagents

Katarzyna M. Kasperowicz-Frankowska ,  Beata Kolesińska ,  Konrad Jastrząbek ,  Zbigniew J. Kamiński 

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

Abstract

Traceless chiral coupling reagents for enantioselective peptide synthesis directly from racemic substrates, developed at Lodz University of Technology, are composed from two fragments: achiral, substitued 1,3,5-triazine derivatives and chiral, quaternary amonium salts. In the previous studies it has been confirmed that application of traceless enantiodifferentaiating coupling reagent leads from racemic substrates to enantiomerically homogenous products with the purity, configuration and the efficiency of coupling predictable on the basis of a single model experiment. This outcome is achived by designing modular structure of enentiodifferentiating reagent with a chiral fragment of reagent acting as stereoselector only in the activation step and its departure after fulfilling its stereoselective function what makes possible to exact prediction of the stereochemical outcome. Thus, all further reaction steps proceeds only in the presence of the achiral module, which is exactly the same as in well known standard achiral triazine reagents [1]. Until now the most impressive stereoselectivities were achieved for reagents derived from alkaloids such as strychnine and brucine. This permit, incorporation of the amino acid into peptide chain in high yields (in the range 85-95%) and high enantiomeric enrichment reaching ee 98-99%. However chiral reagents with alkaloid moiety posses also several drawbacks: alkaloids are highly toxic and occur in only one enantiomeric form, what limits an access to only to one enantiomeric form of the final product (the second one is discriminated). In order to overcome those limitations we attempt to use as a chiral component of traceless coupling reagent, prepared from amino acids derivatives available in both enantiomeric forms. For the best enantioselectivities those derivatives should contain a stereogenic center (except for α-carbon) located on chiral, configurationally stable nitrogen atom (bridged position). In our studies these requirements was reached by applying bicyclic proline derivative in which the amine and carboxyl functions are engaged in the formation an additional ring stabilizing configuration on bridgehead nitrogen atom. Among many bicyclic derivatives, the most promising were 1,3-oxazolidin-5-ones warranted stability of the stereogenic center on proline α-carbon. This particular advantage feature of 1,3-oxazolidin-5-ones was utilized in chirality transfer and chirality selfregeneration processes [3]. Herein, we present the results of our attempts to obtain of 1,3-oxazolidin-5-ones derived from L- and D-proline with a variety of aldehydes and to evaluate their efficiency in the synthesis of new chiral traceless coupling reagents.

Acknowledgments:

This study was supported by the Ministry of Science and High Education under the Reserch Project from National Science Center: project number: 2012/07/N/ST5/01883

References:

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

[2] B. Kolesinska., K. Kasperowicz-Frankowska., J. Fraczyk, Z.J. Kaminski, Helv. Chim. Acta, 95, 2084-2098, 2012.

[3] D. Seebach, A.K. Beck, D.M. Badine, M. Limbach, A. Eschenmoser, A.M. Treasurywala, R. Hobi, Helv. Chim. Acta, 90, 425-471, 2007.

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Presentation: Poster at IX Multidyscyplinarna Konferencja Nauki o Leku, by Katarzyna M. Kasperowicz-Frankowska
See On-line Journal of IX Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2014-03-15 13:09
Revised:   2014-05-02 10:59
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