Fig. 5. Penta-Cys models support strong regioselectivity by DIB in the formation of the Lan staple. (a) For penta-Cys MEK-Cys222 reaction with DIB was monitored using LCMS-ESI-TOF and after 6 hour showed a mixture MEK1-Dha222 (Mobs. = 45 640, Mcalc. = 45 642), MEK1C222 (Mobs. = 45 676, Mcalc. = 45 676) and the sulfonium intermediate MEK1-Sul222 (MEK1CTHT, Mobs. = 45 732, Mcalc. = 45 731). The formation of the first alkylation intermediate MEK1CIB222 (Mcalc. = 45 858) was not observed. Full conversion to MEK1Dha222 was observed after 20 hours. (b) By contrast for regioisomeric penta-Cys MEK-Cys218 only ∼15% conversion of MEK1-C218 (Mobs. = 45 678, Mcalc. = 45 676) to MEK1-Dha218 (Mobs. = 45 642, Mcalc. = 45 642) was observed after 26 hours.
