Synthesis of 2-amino-8-oxodecanoic acids (Aodas) present in natural hystone deacetylase inhibitors.
[reaction: see text] Differently substituted 2-amino-8-oxodecanoic acids (Aodas), present in naturally occurring inhibitors of hystone deacetylase (HDAC), have been prepared using a convergent approach. The configuration in position 2 was derived from enantiomerically pure allylglycine or glutamic acid, whereas the stereochemistry of the substituent in position 9 derived from lactic acid or glyceraldehyde derivatives. Starting from allylglycine, (S)-Aodas, protected at the nitrogen as Boc or Fmoc, were obtained in four steps in about 30% overall yield. These products have been used to prepare a simplified analogue of a natural cyclic tetrapeptide HDAC inhibitor by SPPS.
Rodriquez
Manuela
M
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte don Melillo, 84084 Fisciano, Salerno, Italy.
Bruno
Ines
I
Cini
Elena
E
Marchetti
Mauro
M
Taddei
Maurizio
M
Gomez-Paloma
Luigi
L
D000586:Amination; D003652:Decanoic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D003652:Decanoic Acids; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010455:Peptides; C031071:decanoic acid; D010100:Oxygen