One-Pot Synthesis of Orthogonally Protected Enantiopure S-(Aminoalkyl)cysteine Derivatives§


  • Chiral Aminoalkyl Cation Equivalents, 1

  • Dedicated to the memory of Arno F. Spatola

  • §

    A pioneer of pseudopeptide chemistry


The general synthesis of a new class of non-natural diamino acids, 2-amino-3-[(2′-aminoalkyl)thio]propanoic acids or S-(aminoalkyl)cysteines, is reported. Under the conditions devised, enantiopure N-Boc-protected β-iodoamines, readily generated from proteinogenic α-amino acids, are treated with L-cysteine ethyl ester hydrochloride, using Cs2CO3 as a base. The S-alkylation products, obtained in high yields (96–98 %) and without any detectable traces of accompanying byproducts, are hydrolysed to yield the free carboxyl group. An orthogonal protection is then introduced on the free amino group by treatment with Fmoc-OSu under standard conditions. The inclusion of one of these orthogonally protected diamino acids in a solid-phase growing pentapeptide is also reported. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)