Application of a 6pi-1-azatriene electrocyclization strategy to the total synthesis of the marine sponge metabolite ageladine A and biological evaluation of synthetic analogues.
A 12-step synthesis of the angiogenesis inhibitory marine metabolite ageladine A is reported. The key steps include a 6pi-1-azatriene electrocyclization for formation of the pyridine ring and a Suzuki-Miyaura coupling of N-Boc-pyrrole-2-boronic acid with a chloroimidazopyridine. In addition, an assessment of the biological activity of a variety of synthetic analogues of ageladine A prepared during this synthesis is described.
Meketa
Matthew L
ML
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Weinreb
Steven M
SM
Nakao
Yoichi
Y
Fusetani
Nobuhiro
N
D000818:Animals; D001372:Aza Compounds / Q000737:chemistry*; D003500:Cyclization; D004583:Electrons; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D015394:Molecular Structure; D009792:Oceans and Seas; D011161:Porifera / Q000737:chemistry* / Q000378:metabolism*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
C482289:Ageladine A; D001372:Aza Compounds; D061965:Matrix Metalloproteinase Inhibitors; D011758:Pyrroles; D020782:Matrix Metalloproteinases