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DOI: 10.1055/s-2008-1042670
Solid-Phase Synthesis of N-Aminodipeptides in High Optical Purity
Contributor(s):Yasuhiro Uozumi, Toshimasa SuzukaPublication History
Publication Date:
21 February 2008 (online)
Key words
Mitsunobu reaction - peptides - amino acids - N-aminopeptides
Significance
A solid-phase synthesis of N-aminodipeptide derivatives via the Mitsunobu protocol was developed. Thus, the reaction of (S)-α-hydroxy acids 1 with a Wang resin using DIC followed by the deprotection of the resulting THP esters 2 gave the α-hydroxy esters 3. The Mitsunobu reaction of 3 with (S)-α-aminohydrazine phthalimide 4 afforded the polymer-supported esters 5. TFA-mediated cleavage of 5 gave the N-aminodipeptide derivatives 6a-j in 21-55% yield with excellent diastereomeric purity (>95% de).
Comment
Previously, Jamart-Grégoire and co-workes have reported the efficient synthesis of N-aminodipeptides via the solution-phase Mitsunobu reaction (N. Brosse, A. Grandeury, B. Jamart-Grégoire Tetrahedron Lett. 2002, 43, 2009). This report describes the first solid-phase application of the N-aminodipeptide synthesis via the Mitsunobu protocol. The absolute configuration of 6f was determined to be (S,R) by chemical correlation with the authentic 7f.