| Abstract
| - A convergent total synthesis of khafrefungin, a novel inhibitor of fungal sphingolipid synthesesisolated from the fermentation culture MF6020, has been developed. Alkenylboronic acid 5 andalkenyliodide 6, key fragments for the total synthesis, were prepared from the corresponding achiralaldehydes using tin(II)-catalyzed and Zr(IV)-catalyzed asymmetric aldol reactions, respectively.The Suzuki coupling reaction of these two fragments was successfully performed to give 17 in goodyield. Through the total synthesis, epimerization of the C4 position having a rather highly acidicproton did not occur, indicating that khafrefungin was under strict conformational constraints toprevent the epimerization process. This characteristic stability of khafrefungin has also beendiscussed using semiempirical calculation and synthesis. Finally, khafrefungin derivatives havealso been synthesized, and their antifungal activities have been measured to obtain informationon the structure−activity relationships.
|
