All-trans retinoic acid analogues are effective as both cancer chemopreventive and chemotherapeutic agents, but their dose-limiting toxicity has limited their usage.  The O-glucuronide (4-HPROG) of N-(4-hydroxyphenyl)retinamide (4-HPR) has been found to be a more effective agent, and also has not displayed classical retinoid toxicities in previous studies. Its carbon-linked analog (4-HPRCG) shows even more promise, as does its carbon-linked glucose derivative. Subsequent conversion of the amide linkage in 4-HPRCG to the carbon-linked ketone (4-HBRCG) further improves activity. However, the syntheses of these compounds are lengthy, costly, and require many chromatographic purifications. To this end we have redesigned and streamlined their syntheses for ease of scale up.  These new synthetic routes to the fully carbon-linked 4-HBRCG and 4-HBRCglucose derivatives of 4-HBR using classical carbohydrate chemistry and Suzuki coupling as its key methodologies, will be presented.

Improved synthesis of the C-linked glucoside and glucuronide of  4-hydroxybenzylretinone (4-HBR)

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.