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Totally Synthetic by Paul H. Docherty, 22 August 2006

Total Synthesis of QS-21Aapi


Y.-J. Kim, P. Wang, M. Navarro-Villalobos, B. D. Rohde, J. Mark, D. Y. Gin, J. Am. Chem. Soc. 2006, 11906-11915.

DOI: 10.1021/ja062364i

An amazingly complex molecule - and I’m using an abbreviated form! David Gin and his group have used deft control of their sugar chemistry to build this huge immunoadjuvant, containing an astounding array of functionalities. The steroid-type core is taken completely from quillaic acid, which they use as the starting point for this work. Of couse, they had to complete many glycosidations in this paper, which can look a deceptively simple coupling, but as this table shows, it can be a tricky sort:

I’m not going through the rest of the sugar chemistry, mostly because I’ve seen it before, but it’s really worth looking at. Particularly noteworthy was the use of Nishimura chemistry to build the glucuronic acid unit, and use of Schmidt’s trichloroacetimidate species to couple sugar units. Here’s a summary of the disconnections: