The aziridine-based strategy outlined above could be leveraged again to forge the tryptophan-asparagine linkage. Thus, western fragment 3 was prepared by employing 2-methyl furan as a nucleophile onto aziridine 7. The use of 2-methylfuran as a masked primary amide provided several advantages, notably avoiding undesired side reactions such as epimerization of the b-carbon and imide formation during carboxylic acid activation. The resulting ring-opened product 6 was enlisted directly in a one-pot amide coupling with compound 13. A subsequent Fmoc deprotection and amide coupling with alkyne 5 (Figure ) yielded the cyclization precursor 14 in 56% yield over two steps. Borrowing from the strategy previously developed to access 1, a Larock macrocyclization was employed to form the 17-membered ring, providing 15 in 52% yield using a catalytic quantity of Pd. Due to the increased ring size of 15 relative to 1, no atropisomers were observed for this macrocycle. The protected primary amide functionality was then unveiled via furan oxidation using a Ru catalyst and subsequent aminolysis to afford the completed western fragment 3 in 41% yield. A number of different permutations were tested for the sequence of valine introduction, east-west-fragment coupling, and furan oxidation (an overview is given in Table and in the SI). Approaches to undertake the oxidative cleavage of the furan late-stage after fragment coupling together the 8-mer or 10mer peptide (with/without the Arg-Phe side chain, see Table and SI) led only to decomposition of the substrate, presumably due to interference with the electron-rich imidazole moiety. Coupling of the valine residue to the western fragment 15 followed by oxidative cleavage of the furan/aminolysis, while successful on small scale, resulted in long reaction times (5 days) and diminished yields (< 20%) upon scaleup. In contrast, oxidative cleavage of the furan directly on intermediate 15 proceeded faster (12-24 h) and in higher yield and was thus chosen as the optimal order of operations for this sequence. The ethyl ester moiety of 15 was then hydrolyzed using trimethyltin hydroxide 31 to afford 16 and set the stage for the assembly of the decapeptide.