1997/10/01 by Zhongmin Xu, Charles W. Johannes, Ahmad Houri +4 · 2 citations
Chemistry · Medicine · #Synthetic Organic Chemistry Methods #Carbohydrate Chemistry and Synthesis #Microbial Natural Products and Biosynthesis
paper · doi:10.1021/ja972191k
openalex publication_date 1997/10/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/26
The first enantioselective total synthesis of antifungal agent Sch 38516, also known as fluvirucin B 1, is described. The synthesis includes a convergent asymmetric preparation of amine 17 and acid 18, which are then united to afford diene 62 . Metal-catalyzed transformations play a crucial role in the synthesis of the latter moiety. Of particular note 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 acid 18 . The requisite carbohydrate 38 is synthesized in a highly diastereo- 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 as the chiral auxiliary. Union of the appropriately outfitted carbohydrate 71 and diene 62 through an efficient and diastereoselective glycosylation is followed by a remarkably efficient Mo-catalyzed macrocyclization that proceeds readily at room temperature.