An improved synthesis of the C-linked glucuronide of N-(4-hydroxyphenyl)retinamide.
Retinoic acid analogues such as N-(4-hydroxyphenyl)retinamide (4-HPR) are effective chemopreventatives and chemotherapeutics for numerous types of cancer. The C-linked analogue of the O-glucuronide of 4-HPR (4-HPRCG) has been shown to be a more effective agent. The synthetic route to this molecule has been significantly improved by access to a key C-benzyl-glucuronide intermediate through employment of a Suzuki coupling reaction between an exoanomeric methylene sugar and an aryl bromide. Preliminary evidence shows 4-HPRCG has chemotherapeutic activity.
Walker
Joel R
JR
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus 43210, USA.
Alshafie
Galal
G
Abou-Issa
Hussein
H
Curley
Robert W
RW
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017313:Fenretinide / Q000138:chemical synthesis* / Q000494:pharmacology; D020719:Glucuronides / Q000138:chemical synthesis* / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000517:prevention & control; D011485:Protein Binding; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012176:Retinoids / Q000138:chemical synthesis / Q000494:pharmacology
D000970:Antineoplastic Agents; D020719:Glucuronides; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D017313:Fenretinide