Titanium(IV)-mediated tandem deprotection-cyclodehydration of protected cysteine N-amides: biomimetic syntheses of thiazoline- and thiazole-containing heterocycles.
The scope and limitations of TiCl(4)-mediated Delta(2)-thiazoline synthesis via tandem deprotection-dehydrocyclization of trityl-protected cysteine N-amides is presented. While chemical yields are acceptable (53-96%), the stereochemical outcomes vary on the basis of structural considerations and reaction conditions (22-99% ee). Racemization at the C(2)-exomethine position limits the utility of this method for the formation of a thiazoline within a peptide. Treatment of a tritylated Cys-Cys dipeptide with TiCl(4) afforded the corresponding thiazole-thiazoline heterocycle 12 (38% yield, 97% ee).
Raman
P
P
Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road (MB12), La Jolla, California 92037, USA.
Razavi
H
H
Kelly
J W
JW
D000577:Amides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D018716:Molecular Mimicry; D015394:Molecular Structure; D013844:Thiazoles / Q000737:chemistry*; D014025:Titanium / Q000737:chemistry*
D000577:Amides; D006571:Heterocyclic Compounds; D013844:Thiazoles; D014025:Titanium; D003545:Cysteine