Peptides containing gamma,delta-dihydroxy-L-leucine.
(+/-)-Dehydroleucine was prepared and resolved by porcine kidney acylase. Under the conditions of the Sharpless asymmetric dihydroxylation (SAD), employing AD-mix-alpha, N alpha-carbobenzyloxy-(2S)-4,5-dehydroleucine methyl ester (16) gave rise to a 6.5:1.0 mixture of gamma-lactones 17, favoring the 4R configuration. Such carbamate-protected alpha-amino-gamma-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 C alpha. N alpha-carbobenzyloxy-(2S)-4,5-dehydroleucine (22) was condensed with valine ethyl ester (19) to give dipeptide 23. Treatment of 23 with AD-mix-beta, under the SAD conditions, converted the dehydroleucine residue to gamma,delta-dihydroxyleucine with 4S configuration, as occurs in alloviroidin (3), a natural product isolated from Amanita suballiacea.
Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Benson J
BJ
Edagwa
Carol M
CM
Taylor
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D006900:Hydroxylation; D007930:Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic; D013552:Swine
D010455:Peptides; D010456:Peptides, Cyclic; C068539:dehydroleucine; C040702:viroidin; D000581:Amidohydrolases; C019665:amidase; D007930:Leucine