Orthogonally protected lanthionines: synthesis and use for the solid-phase synthesis of an analogue of nisin ring C.
[structure: see text] Lanthionine, a thioether analogue of cystine, is a key component of the lantibiotics, a family of modified peptides bearing multiple thioether bridges resulting from posttranslational modifications between side chains. It is also used as a conformational constraint in medicinally active peptides. We have explored two synthetic routes to give lanthionine, orthogonally protected with Alloc/allyl and Fmoc groups. One route utilized a carbamate-protected iodoalanine that yielded a mixture of diastereoisomers, and one utilized a trityl-protected iodoalanine, formed via a Mitsunobu reaction, that gave the single desired lanthionine, in complete regio- and diastereoselectivity. We then used this orthogonally protected lanthionine in the solid-phase synthesis of an analogue of a fragment of nisin containing its ring C. The chemoselective deprotection of the allyl and Alloc groups of the incorporated lanthionine unit was followed by regio- and stereoselective cyclization on resin to give the desired lanthionine-bridged peptide.
Bregant
Sarah
S
Department of Chemistry, UCL, Christopher Ingold Laboratories, 20, Gordon Street, London WC1H 0AJ, UK.
Tabor
Alethea B
AB
D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013058:Mass Spectrometry; D019906:Nuclear Magnetic Resonance, Biomolecular; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry
D013440:Sulfides; C001520:lanthionine; D000409:Alanine