Total synthesis of azumamide A and azumamide E, evaluation as histone deacetylase inhibitors, and design of a more potent analogue.
The unprecedented diastereoselective Mannich reaction of a Z-allylsulfoximine was a key step in the total synthesis of the marine natural products azumamide A and E, and an unnatural analogue. Their relative potency as histone deacetylase inhibitors was evaluated and found to correlate with predicted zinc-binding affinity. [reaction: see text]
Wen
Shijun
S
School of Chemistry, University of Southampton, Southampton SO17 1BJ, United Kingdom.
Carey
Krystle L
KL
Nakao
Yoichi
Y
Fusetani
Nobuhiro
N
Packham
Graham
G
Ganesan
A
A
D000498:Allyl Compounds / Q000737:chemistry; D001665:Binding Sites; D001688:Biological Products / Q000138:chemical synthesis / Q000494:pharmacology; D003622:Dapsone / Q000031:analogs & derivatives / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D008956:Models, Chemical; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
D000498:Allyl Compounds; D001688:Biological Products; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; C516228:azumanide A; C516229:azumanide E; C036115:sulfoxone; D003622:Dapsone; D015032:Zinc