An enantioselective synthesis of the Hsp90 inhibitor geldanamycin was achieved in 20 linear steps and 2.0% overall yield from 2-methoxyhydroquinone. The synthesis is highlighted by a regio- and stereoselective hydroboration reaction; a Sc(OTf) 3 /Et 3 SiH-mediated pyran ring-opening reaction; an enantioselective crotylation to simultaneously install the C8–C9 (E)-trisubstituted olefin, the C10 and C11 stereocenters; a chelation-controlled asymmetric metallated acetylide addition; and an intramolecular copper(I)-mediated aryl amidation reaction to close the 19-membered macrolactam.
This paper describes amazingly shortest synthesis for such a complex macrolide. Geldanamycin was synthesized in 20 steps using key steps such as Cu-catalyzed intramolecular amidation. I have used synthetic strategy to synthesize prodrug of geldanamycin with little modification...
Amazingly short synthesis for complex macrolide