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Synthesis and Evaluation of Enantiomeric Purity of Protected α ‐Amino and Peptide Aldehydes
Author(s) -
Mindt Thomas,
Michel Urs,
Dick F.
Publication year - 1999
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/(sici)1522-2675(19991110)82:11<1960::aid-hlca1960>3.0.co;2-2
Subject(s) - chemistry , tetrapeptide , epimer , acetal , aldehyde , stereochemistry , cysteine , yield (engineering) , enantiomer , residue (chemistry) , peptide , peptide synthesis , alanine , amino acid , enzyme , organic chemistry , catalysis , biochemistry , materials science , metallurgy
The synthesis of enantiomerically pure Ac‐Tyr‐Val‐Ala‐Asp(O t Bu)‐H dimethyl acetal (( S )‐ 1 ) is reported, a protected tetrapeptide C‐terminal aldehyde belonging to a class of potent, reversible inhibitors of cysteine proteases ( e.g. , interleukin‐1 β ‐converting enzyme (ICE), also called caspase‐1). The coupling of the precursors Ac‐Tyr‐Val‐Ala‐OH (( S )‐ 8 ) and H‐Asp(O t Bu)‐H dimethyl acetal (( S )‐ 6 ) gave ( S )‐ 1 in a yield of 85%, with epimerization of <2% at the alanine and aspartic‐acid residue. ( S )‐ 6 itself was synthesized in four steps in an overall yield of 83% with an ee >98%.