Ladder polyether synthesis via epoxide-opening cascades using a disappearing directing group.
The combination of a trimethylsilyl group, a Brønsted base, a fluoride source, and a hydroxylic solvent enables the first construction of the tetrad of tetrahydropyran rings found in the majority of the ladder polyether natural products by way of a cascade of epoxide-opening events that emulates the final step of Nakanishi's proposed biosynthetic pathway. The trimethylsilyl group disappears during the course of the cascade, and thus these are the first epoxide ring-opening cascades that afford ladder polyether subunits containing no directing groups at the end of the cascade.
Simpson
Graham L
GL
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, 02139, USA.
Heffron
Timothy P
TP
Merino
Estíbaliz
E
Jamison
Timothy F
TF
D002922:Ciguatoxins / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry*; D004988:Ethers, Cyclic / Q000737:chemistry*; D005663:Furans / Q000737:chemistry; D008968:Molecular Conformation; D008978:Mollusk Venoms; D035964:Oxocins / Q000737:chemistry; D011083:Polycyclic Compounds / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005663:Furans; D008978:Mollusk Venoms; D035964:Oxocins; D011083:Polycyclic Compounds; D011108:Polymers; C482966:adriatoxin; C435770:gambierol; C458159:gymnocin A; C505754:gymnocin-B; D002922:Ciguatoxins; C080898:gambieric acid A; C080900:gambieric acid B; C066632:yessotoxin