Enhancement of Cyclopamine via Conjugation with Nonmetabolic Sugars

The Veratrum alkaloid cyclopamine, an inhibitor of cancer stem cell growth, was used as a representative scaffold to evaluate the inhibitory impact of glycosylation with a group of nonmetabolic saccharides, such as D-threose. In a five-step divergent process, a 32-member glycoside library was created and assayed to determine that glycosides of such sugars notably improved the GI(50) value of cyclopamine while metabolic sugars, such as D-glucose, did not.