|Editor: We originally sent a 1600 x 1200 |
color abstract. Just picture a 15-member
macrolide, densely functionalized with
heterocycles, five stereocenters,
and chelated iron.
Synthetic highlights include: extensive use of Yamamoto's "super-silyl" protecting group, a Sezen C-H arylation / macrocyclization, kilo-scale flash-vacuum pyrolysis (FVP), and enantioselective tributyltin hydride reduction. Efforts to adapt "green" chemical considerations have been made - the penultimate oxidation occurs by swirling flask in open air for three days over twenty equivalents iron oxide catalyst.
This streamlined route utilizes seventeen silica gel purifications, four alumina plugs, two resolutions: D(-)-tartaric acid and 1R(-)-10-camphorsulfonic acid (the expensive ones, sorry!), and a one-pot global HF / Hg / chromic acid deprotection protocol. Overall yield was 0.0008%, as a mixture of diastereomers (brsm).
Two medicinally active methylated analogues will be reported in due course.
Thanks to Derek for the initial inspiration, with a gentle nudge courtesy of Chemjobber.