A New Approach to the Synthesis of Piperazinomycin and Bouvardin:  Facile Access to Cycloisodityrosine via an Intramolecular S_NAr Reaction

TMC‐95A Analogues with Endocyclic Biphenyl Ether Group as Proteasome Inhibitors

“…Synthesis of the Biaryl Ether-Cross-Bridged Cyclic Peptides 3a and 3b. Among the various methods elaborated for the synthesis of biaryl ethers [33 ± 41], the procedure of Beugelmans et al [40] is based on the nucleophilic attack of the phenol on a fluorobenzene derivative activated by an ortho-NO 2 group. This procedure has been successfully applied also in syntheses on solid supports [42].…”

“…Synthesis of Compound 3a in Solution. The key intermediate methyl (S)-3-fluoro-4-nitrophenylalaninate (4) was obtained by the method of Beugelmans et al [40]. As shown in Scheme 1 2 ), the methyl ester 4 was protected as N-Z derivative and saponified to yield 5.…”

“…These differ in their structure from the biaryl-ether compounds of this study merely by the presence of a C-terminal carboxy group as the potential ligand of the enzyme metal ion. [40] (120 mg, 0.495 mmol) in 1,4-dioxane/H 2 O 1 : 1 (15 ml) Z-OSu (136 mg, 0.545 mmol) and NaHCO 3 (46 mg, 0.545 mmol) were added. After stirring at r.t. for 12 h, N-(2-aminoethyl)piperazine (100 ml) was added, and the mixture was stirred for an additional 30 min.…”

Diaryl Ether Formation in the Synthesis of Natural Products

“…[17] Alternatively, the two tyrosine units can be separated by another amino acid, joining them either through the amino group of the phenol moiety and the carboxylic acid group of the aryl ether moiety, as in the angiotensin I converting enzyme inhibitor K-13 (25, Figure 5), or in the opposite sense, as in renieramide (26), the eurypamides (27)(28)(29), and the aminopeptidase B inhibitors OF-4949 I-IV (30). [17] Furthermore, the alkyl chain moieties of the original amino acids can be modified, as in the case of the antifungal agent piperazinomycin (31, Figure 6), [37][38][39][40] and the two aromatic rings can be decorated with additional substituents, such as bromine(s) in the case of the bastadins [17] [32-34, ryanodine (RyR) calcium channel modulators]. …”

“…It should be noted that, despite methodological advances, [42] the selective synthesis of atropisomers is under substrate control. [1,14] The aglycons of glycopeptide antibiotics may be grouped into four different subclasses based on the number and nature of the diaryl ether linkages they contain: type A is exemplified by the aglycons of vancomycin (35; identical to that of balhimycin) and of orienticin (36), type B, such as those of teicoplanin (37) and ristocetin (38), features an additional ring system containing a diaryl ether moiety, whereas type C and type D structures such as complestatin (39) and kistamicin A (40) are each distinguished by a tryptophan-derived biaryl moiety, in the latter case featuring an additional diaryl ether macrocycle ( Figure 7).…”