A strategy for the asymmetric aminohomologation of alpha, beta-dihydroxy aldehydes: application to the synthesis of the southwest tripeptide segment of echinocandin B.
The synthesis of the (2S,3S,4S)-3,4-dihydroxyhomotyrosine amino acid segment, present in echinocandin B, in its activated form ready for peptide coupling is described. The key steps of the approach are the enantioselective AD reaction of 4-methoxycinnamic acid methyl ester, a completely diastereoselective [2 + 2] hydroxyketene-imine cycloaddition, and the TEMPO-assisted cycloexpansion of the resulting 3-hydroxy beta-lactam to the corresponding alpha-amino acid N-carboxy anhydride (NCA). The smooth opening of the latter upon treatment with L-Thr(OSi(t)BuPh(2))OMe and further acylation with the N-Cbz protected L-4-tert-butyldiphenylsilyloxy proline rendered the southwest portion of echinocandin B.
Palomo
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Departamento de Química Orgánica. Facultad de Química. Universidad del País Vasco, Apdo 1072, 20080 San Sebastián, Spain.
Oiarbide
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Landa
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D000447:Aldehydes / Q000737:chemistry*; D000588:Amines / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D054714:Echinocandins; D005656:Fungal Proteins; D009842:Oligopeptides / Q000138:chemical synthesis*; D010455:Peptides; D010456:Peptides, Cyclic; D013057:Spectrum Analysis
D000447:Aldehydes; D000588:Amines; D000900:Anti-Bacterial Agents; D054714:Echinocandins; D005656:Fungal Proteins; D009842:Oligopeptides; D010455:Peptides; D010456:Peptides, Cyclic; C007572:echinocandin B