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Tyrosine alkyl esters as prodrug: the structure and intermolecular interactions of l-tyrosine methyl ester compared to l-tyrosine and its ethyl and n-butyl esters

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Abstract

l-Tyrosine alkyl esters are used as prodrugs for l-tyrosine. Although prodrugs are often designed for their behavior in solution, understanding their solid-state properties is the first step in mastering drug delivery. The crystal structure of l-tyrosine methyl ester has been determined and compared to published structures of l-tyrosine and its ethyl and n-butyl esters. It is almost isostructural with the other esters: it crystallizes in the orthorhombic chiral space group P212121, a = 5.7634(15) Å, b = 12.111(2) Å, c = 14.3713(19) Å, V = 1003.1(4) Å3 with Z′ = 1. Their main packing motif is a C(9) infinite hydrogen-bond chain, but the conformation of l-tyrosine methyl ester is different from the other two: eclipsed versus U-shaped, respectively. The published structure of the ethyl ester, which was incomplete, has been confirmed by X-ray powder diffraction data. Because l-tyrosine methyl ester is very stable (28 years stored at room temperature), and its hydrolysis rate is relatively low, it should be one of the better prodrugs among the alkyl esters of tyrosine.

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Notes

  1. The absolute configuration of TME was considered l, since this was the configuration of the original tyrosine used for the synthesis.

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Acknowledgments

The authors thank Philippe Bénas (Université Paris Descartes) and M. Marsal (Universitat Politècnica de Catalunya) for assistance with single-crystal X-ray diffraction data collection and SEM examinations, respectively. The authors thank the late Nestor Veglio for the powder diffraction data collection. Part of this study was supported by the Spanish grant FIS2008-00837 and by the Catalan government (2008SGR-1251). RC thanks the Generalitat de Catalunya (2007PIV00011) for an invited position at the Universitat Politècnica de Catalunya.

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Authors and Affiliations

  1. Laboratoire de Chimie Physique, EAD Physico-chimie Industrielle du Médicament (former EA4066), Faculté de Pharmacie, Université Paris Descartes, 4, Avenue de l’Observatoire, 75006, Paris, France

    Béatrice Nicolaï, Nathalie Mahé, René Céolin & Ivo B. Rietveld

  2. Grup de Caracterització de Materials (GCM), Departament de Física i Enginyeria Nuclear, Universitat Politècnica de Catalunya, ETSEIB, Diagonal 647, 08028, Barcelona, Spain

    René Céolin, Maria Barrio & Josep-Lluis Tamarit

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  1. Béatrice Nicolaï
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  2. Nathalie Mahé
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  3. René Céolin
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  4. Ivo B. Rietveld
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  5. Maria Barrio
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  6. Josep-Lluis Tamarit
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Correspondence to Ivo B. Rietveld.

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Nicolaï, B., Mahé, N., Céolin, R. et al. Tyrosine alkyl esters as prodrug: the structure and intermolecular interactions of l-tyrosine methyl ester compared to l-tyrosine and its ethyl and n-butyl esters. Struct Chem 22, 649–659 (2011). https://doi.org/10.1007/s11224-010-9723-6

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