Synthesis and histone deacetylase inhibitory activity of largazole analogs: alteration of the zinc-binding domain and macrocyclic scaffold.
Fourteen analogs of the marine natural product largazole have been prepared and assayed against histone deacetylases (HDACs) 1, 2, 3, and 6. Olefin cross-metathesis was used to efficiently access six variants of the side-chain zinc-binding domain, while adaptation of our previously reported modular synthesis allowed probing of the macrocyclic cap group.
Bowers
Albert A
AA
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
West
Nathan
N
Newkirk
Tenaya L
TL
Troutman-Youngman
Annie E
AE
Schreiber
Stuart L
SL
Wiest
Olaf
O
Bradner
James E
JE
Williams
Robert M
RM
D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D008386:Marine Biology; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015032:Zinc / Q000737:chemistry* / Q000494:pharmacology
D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D013844:Thiazoles; C527895:largazole; D015032:Zinc