Synthetic studies toward the total synthesis of ristocetin A

On the way toward the total synthesis of ristocetin A, the prerequisite E ring arylserine ruthenium complex 2.47 and F ring arylglycine 3.34 were prepared by utilizing Sharpless asymmetric dihydroxylation and Sharpless asymmetric aminohydroxylation methodologies, respectively.*; As a model study, a convenient synthesis of the fully functionalized DEF ring system 3.1 of ristocetin A was developed by using a ruthenium-promoted intramolecular S_NAr reaction under conditions that were mild enough to avoid epimerization, when the C-terminus of the central amino acid D was protected as its N-methylamide. Indeed, the regiospecific macrocyclization in favor of the 16-membered ring provided an efficient approach to the final DEFG ring system of ristocetin A as well as teicoplanin.*; In addition, for an approach to the more advanced system containing a final 14-membered ring of ristocetin A, it was demonstrated that intermolecular etherification between 4.17 and arylglycinol-ruthenium complex 4.47 can be accomplished.*; *Please refer to dissertation for diagrams.