American Chemical Society
Browse
ol061439k_si_001.pdf (1.94 MB)

De Novo Asymmetric Synthesis of Milbemycin β3 via an Iterative Asymmetric Hydration Approach

Download (1.94 MB)
journal contribution
posted on 2006-08-31, 00:00 authored by Miaosheng Li, George A. O'Doherty
The enantioselective synthesis of the spiroketal/macrolide natural product milbemycin β3 has been achieved in 22 steps and 2.8% overall yield from an achiral dienoate. The spiroketal ring system was installed by three sequential asymmetric hydrations followed by sprioketalization. Both the absolute and relative stereochemistry of milbemycin β3 was introduced by two Sharpless asymmetric dihydroxylations, two π-allylpalladium-catalyzed reductions, and an iridium-catalyzed hydrogen migration/Claisen rearrangement to install the C-12 stereocenter.

History