Peptides Containing γ,δ-Dihydroxy-l-leucine

(±)-Dehydroleucine was prepared and resolved by porcine kidney acylase. Under the conditions of the Sharpless asymmetric dihydroxylation (SAD), employing AD-mix-α, Nα-carbobenzyloxy-(2S)-4,5-dehydroleucine methyl ester (16) gave rise to a 6.5:1.0 mixture of γ-lactones 17, favoring the 4R configuration. Such carbamate-protected α-amino-γ-hydroxylactones are not recommended as intermediates for peptide synthesis, since model studies showed that lactone 13 was unreactive toward amines. Moreover, the lactone ring could not be opened hydrolytically without epimerization at Cα. Nα-Carbobenzyloxy-(2S)-4,5-dehydroleucine (22) was condensed with valine ethyl ester (19) to give dipeptide 23. Treatment of 23 with AD-mix-β, under the SAD conditions, converted the dehydroleucine residue to γ,δ-dihydroxyleucine with 4S configuration, as occurs in alloviroidin (3), a natural product isolated from Amanita suballiacea.