Synthesis of neolamellarin A, an inhibitor of hypoxia-inducible factor-1.
Neolamellarin A, a metabolite isolated from the sponge Dendrilla nigra, was found to inhibit hypoxia-inducible factor-1 (HIF-1) activation by 26% at 10 microM concentration and inhibition of HIF-1 has become a major antitumor molecular target. Herein the first synthesis of neolamellarin A is described. The synthetic strategy features the condensation of vinylogous amide with aminomalonate to construct the 3,4-bis(4-methoxyphenyl)-1H-pyrrole core and the subsequent acylation and deprotection rendered the target compound in 18% over all yield.
Arafeh
Khaled M
KM
Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia.
Ullah
Nisar
N
D000215:Acylation; D000577:Amides / Q000737:chemistry; D000818:Animals; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors*; D007202:Indicators and Reagents; D011161:Porifera / Q000737:chemistry; D011758:Pyrroles
D000577:Amides; D051793:Hypoxia-Inducible Factor 1; D007202:Indicators and Reagents; D011758:Pyrroles; C543768:neolamellarin A