Thioether macrocycles of the microbisporicins via reductive desulfurization. Issue 31 (2nd August 2018)

• Record Type: Journal Article
• Authors: Kutty, Samuel K.; Lutz, Joshua A.; Felder, Simon; Hahn, Philip; Taylor, Carol M.
• Is Part Of: Tetrahedron. Volume 74:Issue 31(2018)
• Page Start: 4247
• Page End: 4258
• Publication Date: 2018-08-02
• Subjects: Lantibiotic -- Thioether -- Peptide synthesis -- Desulfurization; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2018.06.050
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The microbisporicins are the most potent lantibiotics isolated to-date. Cyclic tetra-, hexa- and octapeptides, inspired by this family of antimicrobial agents, have been synthesized from linear peptides. Generalized reaction conditions are reported for the two-step conversion of linear peptides to thioether macrocycles: formation of a disulfide followed by reductive desulfurization. 1 H NMR analysis of the reduction reaction mixture indicated the intermediacy of a dehydroalanine when excess hexamethylphosphorus triamide (HMPT) was employed for the reduction. Maintaining a stoichiometric amount of HMPT, in dilute methanolic solution, gave the corresponding thioethers, retaining stereochemical integrity. Graphical abstract: Image 1