新产品编号:1660027
Chemical Name: 2(R)-[2,6-Dibromo-4-(6-bromobenzo[b]naphtho[2,3-d]furan-11-yl)phenoxy]-3-phenylpropionic acid
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:Condensation of salicylaldehyde (I) with 2-bromoacetophenone (II) produced benzofuranyl phenyl ketone (III),which was reduced to 2-benzyl benzofuran (IV) under Wolff-Kishner conditions.Subsequent Friedel-Crafts acylation of (IV) with anisoyl chloride (V) employing SnCl4 afforded ketone (VI).Methyl ether cleavage in (VI) with concomitant intramolecular cyclization,followed by dehydration by means of BBr3 gave rise to benzo naphthofuran (VII).This was brominated in AcOH to yield tribromo derivative (VIII).Mitsunobu coupling of (VIII) with (S)-methyl-2-hydroxy-3-phenylpropionate (IX) furnished ether (X).Finally,the methyl ester group of (X) was hydrolyzed with KOH.
📌 参考资料/链接：
参考文献标题:11-Aryl-benzo[b]naphtho[2,3-d]furans and 11-aryl-benzo[b]naphtho[2,3-d]thiophenes useful in the treatment of insulin resistance and hyperglycemia
文献作者:Dietrich,A.J.; Wrobel,J.E.; Li,Z.(American Home Products Corp.)
参考来源:WO 9958521
📄 详细内容
合成路线:Condensation of salicylaldehyde (I) with 2-bromoacetophenone (II) produced benzofuranyl phenyl ketone (III),which was reduced to 2-benzyl benzofuran (IV) under Wolff-Kishner conditions.Subsequent Friedel-Crafts acylation of (IV) with anisoyl chloride (V) employing SnCl4 afforded ketone (VI).Methyl ether cleavage in (VI) with concomitant intramolecular cyclization,followed by dehydration by means of BBr3 gave rise to benzo naphthofuran (VII).This was brominated in AcOH to yield tribromo derivative (VIII).Mitsunobu coupling of (VIII) with (S)-methyl-2-hydroxy-3-phenylpropionate (IX) furnished ether (X).Finally,the methyl ester group of (X) was hydrolyzed with KOH.
参考文献标题:PTP1B inhibition and antihyperglycemic activity in the ob/ob mouse model of novel 11-arylbenzo[b]naphto[2,3-d]furans and 11-arylbenzo[b]naphtho[2,3-d]thiophenes
文献作者:Wrobel,J.; Sredy,J.; Moxham,C.; Dietrich,A.; Li,Z.; Sawicki,D.R.; Seestaller,L.; Wu,L.; Katz,A.; Sullivan,D.; Tio,C.; Zhang,Z.Y.
参考来源:J Med Chem 1999,42(17),3199-3202