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Selektive Amidspaltung bei Peptiden mit α,α‐disubstituierten α‐Aminosäuren
Author(s) -
Wipf Peter,
Heimgartner Heinz
Publication year - 1987
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19870700213
Subject(s) - chemistry , dipeptide , amide , epimer , hydrolysis , amino acid , stereochemistry , yield (engineering) , racemization , cleavage (geology) , medicinal chemistry , organic chemistry , biochemistry , materials science , geotechnical engineering , fracture (geology) , engineering , metallurgy
Selective Amide Cleavage in Peptides Containing α,α‐Disubstituted α‐Amino Acids A new synthesis of dipeptides with terminal α,α‐disubstituted α‐amino acids, using 2,2‐disubtituted 3‐amino‐2 H ‐azirines 1 as amino‐acid equivalents, is demonstrated. The reaction of 1 with N‐protected amino acids leads to the corresponding dipeptide amides in excellent yield. It is shown that the previously described selective hydrolysis (HCl, toluene, 80°, or HCl, MeCN/H 2 O, 80°) of the terminal amide group results in an extensive epimerization of the second last amino acid. An acid‐catalyzed enolization in the intermediate oxazole‐5(4 H )‐ones is responsible for this loss of configurational integrity. In the present paper, a selective hydrolysis of the terminal amide group under very mild conditions is described: In 3 N HCl (THF/H 2 O 1:1), the dipeptide N , N ‐dimethylamides or N ‐methytlanilides are hydrolized at 25–35° to the optically pure dipeptides in very good yield.