Intramolecular O-arylation of phenols with phenylboronic acids: application to the synthesis of macrocyclic metalloproteinase inhibitors.
[reaction: see text]. The copper acetate mediated intramolecular O-arylation of phenols with phenylboronic acid pseudopeptides is the key step in the preparation of macrocyclic biphenyl ether hydroxamic acid inhibitors of collagenase 1 and gelatinases A and B. The intramolecular macrocyclization was found to be mild and tolerant of common chemical functionality. This methodology should provide a general route to macrocyclic biphenyl ethers.
Chemical and Physical Sciences, The DuPont Pharmaceuticals Company, Experimental Station, Wilmington, Delaware 19880-E500-1604B, USA. carl.p.decicco@dupontpharma.com
C P
CP
Decicco
Y
Y
Song
D A
DA
Evans
D001897:Boronic Acids / Q000737:chemistry*; D017364:Collagenases; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D015195:Drug Design; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry
D001897:Boronic Acids; D061965:Matrix Metalloproteinase Inhibitors; D010636:Phenols; D011480:Protease Inhibitors; D003300:Copper; D017364:Collagenases; C417249:collagenase 1; C010686:benzeneboronic acid