425399-85-5Relevant academic research and scientific papers
Biomimetic studies on the mechanism of stereoselective lanthionine formation
Zhu, Yantao,Gieselman, Matt D.,Zhou, Hao,Averin, Olga,Van der Donk, Wilfred A.
, p. 3304 - 3315 (2007/10/03)
Selenocysteine derivatives are useful precursors for the synthesis of peptide conjugates and selenopeptides. Several diastereomers of Fmoc-3-methyl-Se-phenylselenocysteine (FmocMeSec(Ph)) were prepared and used in solid phase peptide synthesis (SPPS). Once incorporated into peptides, the phenylselenide functionality provides a useful handle for the site and stereospecific introduction of E- or Z-dehydrobutyrine residues into peptide chains via oxidative elimination. The oxidation conditions are mild, can be performed on a solid support, and tolerate functionalities commonly found in peptides, including variously protected cysteine residues. Dehydropeptides containing unprotected cysteine residues undergo intramolecular stereoselective conjugate addition to afford cyclic lanthionines and methyllanthionines, which have the same stereochemistry as found in lantibiotics, a family of ribosomally synthesized and post-translationally modified peptide antibiotics. The observed stereoselectivity is shown to originate from a kinetic rather than a thermodynamic preference.
Biomimetic stereoselective formation of methyllanthionine.
Zhou, Hao,van der Donk, Wilfred A
, p. 1335 - 1338 (2007/10/03)
Fmoc-(2R,3S)-3-methyl-Se-phenylselenocysteine was used for the synthesis of dehydrobutyrine (Dhb)-containing peptides. Biomimetic cyclization via Michael addition of Cys to a Dhb yielded the B-ring of the lantibiotic subtilin as a single diastereomer. The methyllanthionine product was shown to have the natural configuration by preparation of the authentic stereoisomer. The formation of a single isomer suggests that the prepeptide has a strong intrinsic preference for the stereochemistry observed in lantibiotics. [reaction: see text]
