CNRS, BioCIS, CY Cergy Paris Université, 95000 Cergy Pontoise, France.
CNRS, BioCIS, Université Paris-Saclay, 92290 Châtenay-Malabry, France.
Org Lett. 2021 Jan 15;23(2):382-387. doi: 10.1021/acs.orglett.0c03880. Epub 2020 Dec 28.
The straightforward synthesis of enantiopure 5-()-and 5-()-trifluoromethylproline is reported. The key steps are a Ruppert-Prakash reagent addition on l-pyroglutamic esters followed by an elimination reaction and a selective reduction. The solution-phase and solid-phase incorporation of this unprotected enantiopure fluorinated amino acid in a short peptide chain was demonstrated. Compared to proline, the CF group provides a decrease of the to amide bond isomerization energy and an increase of the conformer population.
报告了对映纯 5-()-和 5-()-三氟甲基脯氨酸的直接合成。关键步骤是在手性 l-焦谷氨酸酯上进行 Ruppert-Prakash 试剂加成，然后进行消除反应和选择性还原。证明了这种未保护的手性纯氟代氨基酸在短肽链中的溶液相和固相掺入。与脯氨酸相比，CF 基团降低了 到酰胺键异构体化的能量，增加了 构象的比例。
