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(L)-(Trimethylsilyl)alanine synthesis exploiting hydroxypinanone-induced diastereoselective alkylation

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Abstract

A new and efficient synthesis of (L)-(trimethylsilyl)alanine (TMSAla) with suitable protection for use in Solid Phase Peptide Synthesis (SPPS) has been accomplished starting from glycine tert-butyl ester and using hydroxypinanone as chiral inductor. The silylated side chain was introduced by alkylation of the Schiff base intermediate with iodomethyl(trimethylsilane) at −78 °C. Among the different synthetic routes that were tested including several chiral inductors and different Schiff bases, this strategy was selected and afforded (L)-TMSAla in good chemical overall yield with 98 % ee.

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Acknowledgments

We thank ANRT and Medincell S.A for financial support (Cifre Grant of Adeline René).

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Authors and Affiliations

  1. IBMM, UMR-CNRS-5247, Universités Montpellier I and II, Place Eugène Bataillon, 34095, Montpellier, France

    A. René, J. Martinez & F. Cavelier

  2. Chirosciences, ISm2,UMR-7313, Aix-Marseille Université, Avenue Escadrille Normandie Niémen, 13397, Marseille, France

    N. Vanthuyne

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  1. A. René
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  2. N. Vanthuyne
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  3. J. Martinez
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  4. F. Cavelier
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Correspondence to F. Cavelier.

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René, A., Vanthuyne, N., Martinez, J. et al. (L)-(Trimethylsilyl)alanine synthesis exploiting hydroxypinanone-induced diastereoselective alkylation. Amino Acids 45, 301–307 (2013). https://doi.org/10.1007/s00726-013-1492-2

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