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 segmen t, present in echinocandin B, in its activated form ready for peptide coupl ing is described. The key steps of the approach are the enantioselective AD reaction of 4-methoxycinnamic acid methyl ester, a completely diastereosel ective [2 + 2] hydroxyketene-imine cycloaddition, and the TEMPO-assisted cy clo-expansion of the resulting 3-hydroxy beta-lactam to the corresponding a lpha-amino acid N-carboxy anhydride (NCA). The smooth opening of the latter upon treatment with L-Thr((OSiBuPh2)-Bu-t)OMe and further acylation with t he N-Cbz protected L-4-tert-butyldiphenylsilyloxy proline rendered the sout hwest portion of echinocandin B.