Regioselective Conversion of the Secondary Hydroxyl Groups of D-Glucuronic Acid without the Requirement of O-Protecting Groups

• Published in: Chemistry : a European journal 2005-10, Vol.11 (21), p.6407-6413
• Main Authors: Ágoston, Károly, Geyer, Armin
• Format: Article
• Language: English
• Subjects: Bridged Bicyclo Compounds - chemistry; carbohydrates; Crystallography, X-Ray; Depsipeptides - chemical synthesis; Depsipeptides - chemistry; glucose; Glucuronic Acid - chemistry; hapalosin; Hydroxyl Radical - chemistry; Indicators and Reagents; Lactams - chemical synthesis; Lactams - chemistry; Lactones - chemical synthesis; Lactones - chemistry; Mesylates; Models, Molecular; Molecular Conformation; synthetic methods; thiazolidinlactams
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200500515

Trifluoromethanesulfonic acid anhydride (triflic acid anhydride) transforms the bicyclic thiazolidinlactam 1 a into the crystalline elimination product 2, in which all four secondary hydroxyl groups of 1 a are differently functionalized. Compound 2 can then add nucleophiles with high chemo‐ and stereoselectivity. Altogether, the four secondary hydroxyl groups of D‐glucuronic acid are selectively transformed without the need for any O‐protecting groups. Minimizing the number of O‐protecting groups is a prerequisite for the use of sugar scaffolds in molecular libraries. The hapalosin analogues 15, 16, 19, and 22 outline the strategy towards O‐diversified glucose derivatives. Synthesis of hapalosin analogues: The combination of protection and activation in a single functional group, for example, an epoxide or an active ester, allows the straightforward modification of sugar hydroxyl groups (see picture). Thus, four secondary hydroxyl groups of a glucose derivative can be diversified without the use of hydroxy protecting groups.