Synthesis and Configurations of (-)-Furospongin-1 and (+)-Dihydrofurospongin-2

The long-known furanoterpenes furospongin-1 and dihydrofurospongin-2 were synthesized for the first time using a chiral-pool-based route in an effort to secure the previous configurational assignments. The key C-11 stereogenic centre was taken from D-mannose, and the C-13 alkyl centre was installed exploiting the chirality of mannose. Due to deprotonation and/or enolization of the building blocks used, introduction of the furan moieties was problematic, and so some reactions had to be avoided. The trisubstituted alkene was most satisfactorily constructed using a Julia-Kocienski olefination in 1,2-dimethoxyethane, with the best (E)/(Z) ratio achieved using a secondary sulfone. The synthetic samples not only provided the first unequivocal piece of evidence for the C-13 configuration of both natural products, but also confirmed the absolute configuration at C-11 of furospongin-1.