Total synthesis of piericidin A1 and B1.
The first total syntheses of piericidin A1 and B1 are disclosed and unambiguously establish the relative and absolute stereochemistry of the natural products by an approach that will facilitate the synthesis of a series of analogues. Central to the approach is an inverse electron demand Diels-Alder reaction of a N-sulfonyl-1-aza-1,3-butadiene with tetramethoxyethene followed by Lewis acid-promoted aromatization used to assemble the functionalized pyridine core. Additional key elements in the convergent approach include the use of an anti-aldol reaction to install the C9 and C10 relative and absolute stereochemistry, a modified Julia olefination for formation of the C5-C6 trans double bond with convergent assemblage of the side chain, and a penultimate heterobenzylic Stille cross-coupling reaction of the pyridyl core with the fully elaborated side chain.
Schnermann
Martin J
MJ
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Boger
Dale L
DL
D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry
D011725:Pyridines; C081410:piericidin B5; C100213:piericidin A