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

Matthew L Meketa; Steven M Weinreb; Yoichi Nakao; Nobuhiro Fusetani

doi:10.1021/jo0707232

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

J Org Chem. 2007 Jun 22;72(13):4892-9. doi: 10.1021/jo0707232. Epub 2007 Jun 1.

Authors

Matthew L Meketa¹, Steven M Weinreb, Yoichi Nakao, Nobuhiro Fusetani

Affiliation

¹ Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.

PMID: 17539689
DOI: 10.1021/jo0707232

Abstract

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.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Aza Compounds / chemistry*
Cyclization
Electrons*
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinases / metabolism
Molecular Structure
Oceans and Seas
Porifera / chemistry*
Porifera / metabolism*
Pyrroles / chemical synthesis*
Pyrroles / chemistry
Pyrroles / metabolism
Pyrroles / pharmacology*

Substances

Ageladine A
Aza Compounds
Matrix Metalloproteinase Inhibitors
Pyrroles
Matrix Metalloproteinases