APPLICATIONS OF ZR-CATALYZED CARBOMAGNESATION AND MO-CATALYZED MACROCYCLIC RING CLOSING METATHESIS IN ASYMMETRIC-SYNTHESIS - ENANTIOSELECTIVE TOTAL SYNTHESIS OF SCH-38516 (FLUVIRUCIN B-1)

The first enantioselective total synthesis of antifungal agent Sch 385 16, also known as fluvirucin B-1, is described. The synthesis includes a convergent asymmetric preparation of amine 17 and acid 18, which ar e then united to afford diene 62. Metal-catalyzed transformations play a crucial role in the synthesis of the latter moiety. Of particular n ote are the diastereo-and enantioselective Zr-catalyzed alkylations, a tandem Ti-and Ni-catalyzed process that constitutes a hydrovinylation reaction, and a Ru-catalyzed alcohol oxidation to afford carboxylic a cid 18. The requisite carbohydrate 38 is synthesized in a highly diast ereo-and enantioselective fashion. Optical purity of the carbohydrate moiety arises from the use of the asymmetric dihydroxylation method of Sharpless; diastereochemical control is achieved through a selective dipolar [3 + 2] cycloaddition with a readily available amine serving a s the chiral auxiliary. Union of the appropriately outfitted carbohydr ate 71 and diene 62 through an efficient and diastereoselective glycos ylation is followed by a remarkably efficient Mo-catalyzed macrocycliz ation that proceeds readily at room temperature.