Lanthionine macrocyclization by in situ activation of serine.
The present report details a straightforward, solid-phase approach to cyclolanthionine peptides. After stepwise assembly of the linear sequence and transformation of a single exposed serine to bromoalanine using P(Ph)3/CBr4, the detritilation of a cysteine side-chain sets the stage for a base-promoted macrocyclization. The entire procedure can be carried out in a solid-phase vessel using conventional 9-fluorenylmethyloxycarbonyl/tert-butyl-based chemistry and is amenable to automated format. The utility of this novel procedure is demonstrated by the synthesis of two previously reported lanthionine-containing cyclic peptides.
Mayer
J P
JP
Amgen Inc., Boulder, Colorado 80301, USA. john.mayer@amgen.com
Zhang
J
J
Groeger
S
S
Liu
C F
CF
Jarosinski
M A
MA
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D000598:Amino Acids, Cyclic / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D015394:Molecular Structure; D017421:Sequence Analysis; D012694:Serine / Q000737:chemistry*; D013440:Sulfides
D000598:Amino Acids, Cyclic; D013440:Sulfides; D012694:Serine; C001520:lanthionine; D000409:Alanine