title: Enantioselective synthesis of (2R, 3S)- and (2S, 3R)-4,4,4-trifluoro-N-Fmoc-O-tert-butyl-threonine and their racemization-free incorporation into oligopeptides via solid-phase synthesis.
abstract: An efficient method for the enantioselective synthesis of (2R, 3S)- and (2S, 3R)-4,4,4-trifluoro-N-Fmoc-O-tert-butyl-threonine on multigram scales was developed. Absolute configurations of the two stereoisomers were ascertained by X-ray crystallography. Racemization-free coupling conditions for the incorporation of tfT into oligopeptides were then explored. For solution-phase synthesis, tfT racemization was not an issue under conventional coupling conditions. For solid-phase synthesis, the following conditions were identified to achieve racemization-free synthesis: if tfT (3.0 equiv) was not the first amino acid to be linked to the resin (1.0 equiv), the condition is 2.7 equiv DIC/3.0 equiv HOBt as the coupling reagent at 0 degrees C for 20 h; if tfT (3.0 equiv) was the first amino acid to be linked to the resin (1.0 equiv), then 1.0 equiv of CuCl(2) needs to be added to the coupling reagent.
authors: Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA.
authors: Nu
authors: N
authors: Xiao
authors: Zhong-Xing
authors: ZX
authors: Jiang
authors: Y Bruce
authors: YB
authors: Yu
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D020650:Combinatorial Chemistry Techniques; D005449:Fluorenes / Q000138:chemical synthesis* / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013912:Threonine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: C526777:4,4,4-trifluoro-N-fluorenylmethoxycarbonyl-O-tert-butylthreonine; D005449:Fluorenes; D009842:Oligopeptides; D013912:Threonine
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