APPLICATIONS OF AN ASYMMETRIC [2 + 2]-PHOTOCYCLOADDITION - TOTAL SYNTHESIS OF (-)-ECHINOSPORIN - CONSTRUCTION OF AN ADVANCED 11-DEOXYPROSTAGLANDIN INTERMEDIATE

The first total synthesis of the novel antitumor metabolite (-)-echinosporin (1) has been achieved. Asymmetric [2 + 21-photocycloaddition of dihydrofuran acetonide (+)-8 to 2-cyclopentenone (7) constituted the cornerstone of the synthetic strategy. Mitsunobu lactonization of hemiacetal acid 43 generated the tricyclic framework of 1, which embodies a strain energy of ca. 17 kcal/mol as estimated by MNDO calculations. The successful synthetic venture permitted assignment of the absolute configuration of echinosporin. Construction of the Corey 11-deoxyprostaglandin intermediate (+)-49 further demonstrated the utility of (+)-8 as a chiral building block.