A beta-lactam-based stereoselective access to beta,gamma-dihydroxy alpha-amino acid-derived peptides with either alpha,beta-like or unlike configurations.
A concise access to alpha,beta-dihydroxy alpha-amino acid-derived N-carboxy anhydrides (NCAs) with either like or unlike relative configuration is described. The key steps of the synthetic route are the preparation of the nonracemic 4-alkenyl beta-lactams, through either Horner-type olefination of a common 4-formyl beta-lactam or the Corey-Winter alkene synthesis applied to 4-dihydroxyalkyl beta-lactams, followed by the Sharpless AD reaction, and a subsequent ring expansion of the corresponding 4-substituted 3-hydroxy beta-lactams promoted by TEMPO. The opening of thus-prepared NCAs upon treatment with different O- and N-nucleophiles, including alpha-amino esters which lead to peptides, has also been studied under various reaction conditions.
Palomo
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C
Departamento de Química Orgánica I, Facultad de Química, Universidad del País Vasco, Apdo 1072, 20080 San Sebastián, Spain. qoppanic@sc.ehu.es
Oiarbide
M
M
Landa
A
A
Esnal
A
A
Linden
A
A
D000596:Amino Acids / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D013057:Spectrum Analysis; D047090:beta-Lactams / Q000737:chemistry*
D000596:Amino Acids; D010455:Peptides; D047090:beta-Lactams