Differently substituted 2-amino-8-oxodecanoic acids (Aodas), present in naturally occurring inhibitors of histone deacetylase (HDAC), have been prepd. using a convergent approach. The configuration in locant 2 of Aodas was derived from enantiomerically pure allylglycine or glutamic acid, whereas the stereochem. of the substituent in locant 9 was derived from either (R)- or (S)-lactic acid or its glyceraldehyde deriv. Starting from allylglycine, (2S,9S)- and (2S,9R)-Aodas, protected at the nitrogen as Boc or Fmoc, were obtained in four steps in about 30% overall yield. (2S,9R)-Aoda was used to prep. a cyclic peptide I, a simplified analog of a natural cyclic tetrapeptide inhibitor of histone deacetylase, by solid-phase peptide synthesis. I showed an IC50 = 10 mM when tested against class III HDACs.
Synthesis of 2-Amino-8-oxodecanoic Acids (Aodas) Present in Natural Histone Deacetylase Inhibitors.
RODRIQUEZ, Manuela;BRUNO, Ines;
2006-01-01
Abstract
Differently substituted 2-amino-8-oxodecanoic acids (Aodas), present in naturally occurring inhibitors of histone deacetylase (HDAC), have been prepd. using a convergent approach. The configuration in locant 2 of Aodas was derived from enantiomerically pure allylglycine or glutamic acid, whereas the stereochem. of the substituent in locant 9 was derived from either (R)- or (S)-lactic acid or its glyceraldehyde deriv. Starting from allylglycine, (2S,9S)- and (2S,9R)-Aodas, protected at the nitrogen as Boc or Fmoc, were obtained in four steps in about 30% overall yield. (2S,9R)-Aoda was used to prep. a cyclic peptide I, a simplified analog of a natural cyclic tetrapeptide inhibitor of histone deacetylase, by solid-phase peptide synthesis. I showed an IC50 = 10 mM when tested against class III HDACs.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
