Total synthesis of the lycopodium alkaloid (+)-serratezomine A.
The first total synthesis of (+)-serratezomine A is described. Key aspects of the synthesis include (a) the first deployment of free-radical-mediated vinyl amination (an intramolecular alkyne aminostannation) in a complex target synthesis, (b) the use of a beta-stannyl enamine as the lynchpin for convergent assembly of the natural product backbone, (c) the use of an oxidative allylation promoted by cerium(IV) (CAN) to establish the all-carbon quaternary chiral center with the proper configuration, and (d) an intramolecular substitution reaction to form the sensitive bridging lactone. Overall, 15 steps (longest linear sequence) are required to prepare the natural product from a commercially available aldehyde, and assembly of the contiguous array of six stereocenters is accomplished with high stereocontrol.
Chandra
Aroop
A
Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235-1822, USA.
Pigza
Julie A
JA
Han
Jeong-Seok
JS
Mutnick
Daniel
D
Johnston
Jeffrey N
JN
D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry; D032502:Lycopodium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
D007212:Indolizines; C415194:serratezomine A