Evolution of a total synthesis of (-)-kendomycin exploiting a Petasis-Ferrier rearrangement/ring-closing olefin metathesis strategy.
A convergent stereocontrolled total synthesis of (-)-kendomycin (1) has been achieved. The synthesis proceeds with a longest linear sequence of 21 steps, beginning with commercially available 2,4-dimethoxy-3-methylbenzaldehyde (12). Highlights of the synthesis include an effective Petasis-Ferrier union/rearrangement tactic to construct the sterically encumbered tetrahydropyran ring, a ring-closing metathesis to generate the C(4a-13-20a) macrocycle, an effective epoxidation/deoxygenation sequence to isomerize the C(13,14) olefin, and a biomimetic quinone-methide-lactol assembly to complete the synthesis.
Smith
Amos B
AB
Department of Chemistry, Monell Chemical Senses Center, and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu
Mesaros
Eugen F
EF
Meyer
Emmanuel A
EA
D000475:Alkenes / Q000737:chemistry*; D003500:Cyclization; D009285:Naphthoquinones; D017828:Rifabutin / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000475:Alkenes; D009285:Naphthoquinones; C485395:kendomycin; C477935:sterekunthal A; D017828:Rifabutin