Studies toward the total synthesis of ristocetin A aglycone using arene–ruthenium complexes as SNAr substrates: construction of an advanced tricyclic intermediate

Abstract

Ruthenium-mediated S N Ar reactions are used to construct the diaryl ether linkages in two key intermediates for a projected total synthesis of the aglycone of ristocetin A.

Diaryl Ether Formation in the Synthesis of Natural Products

“…[105,107] Several diaryl ethers related to vancomycin (35), [106] orienticin C (36), [113] teicoplanin (37), [110] and complestatin (39) [115] were thus accessible by this method without any epimerization of sensitive amino acids during the coupling or photochemical diaryl ether liberation steps. The method has been successfully employed in the total syntheses of K-13 (25) and OF-4949-III (30) [108,111,117] and in the synthesis of an advanced intermediate in the synthesis of ristocetin (38) [107,109,112,114] (Table 7). The last of these is perhaps more important because it precludes the use of this method for the construction of many halogenated natural products, such as bastadins and several glycopeptide antibiotics.…”

Methods for the Chemical Synthesis of Noncoded α‐Amino Acids found in Natural Product Peptides

“…Next, intermolecular aromatic nucleophilic substitution (S N Ar) of the two fragments resulted in optimized yield of 70% for diaryl ether 247 formation (Scheme 5.59). In other work toward the diaryl ether fragment, Pearson et al have explored the application of arene-ruthenium complexes as S N Ar substrates [278]. …”

Synthesis of a 30-Membered Macrocycle Incorporating Two Ruthenium Sandwich Complexes

“…There has also been intense work on the total synthesis of Ru-complexed vancomycin-type diaryl ethers, in particular towards ristotecin A by the Pearson group [17,18]. We have developed a universal We also developed an efficient protocol for the purification of the charged complexes by semipreparative HPLC.…”