Хіральне розділення похідних β-СF3-α-проліну

An operationally simple and scalable preparation of all four stereoisomers of N-Boc β-CF₃-α-proline in high enantiomeric purity is described. Acylation of racemic cis-β-CF₃-α-proline with (S)-2-phenylpropanoic acid under standard amide coupling conditions affords a pair of diastereomeric amides that...

Повний опис

Збережено в:
Бібліографічні деталі
Дата:2025
Автори: Redka, Mykhailo O., Liashuk, Oleksandr S., Kondratov, Ivan S., Grygorenko, Oleksandr O.
Формат: Стаття
Мова:Англійська
Опубліковано: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2025
Теми:
Онлайн доступ:https://bioorganica.com.ua/index.php/journal/article/view/118
Теги: Додати тег
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Назва журналу:Ukrainica Bioorganica Acta

Репозитарії

Ukrainica Bioorganica Acta
Опис
Резюме:An operationally simple and scalable preparation of all four stereoisomers of N-Boc β-CF₃-α-proline in high enantiomeric purity is described. Acylation of racemic cis-β-CF₃-α-proline with (S)-2-phenylpropanoic acid under standard amide coupling conditions affords a pair of diastereomeric amides that can be resolved by normal-phase column chromatography on multi-gram scale (up to 37 g per isomer). Subsequent acidic cleavage of the N,C-protection groups induce complete epimerization at the amino acid center; N-Boc protection of the resulting mixture followed by chromatographic separation provides individual N-Boc β-CF₃-α-proline stereoisomers with ee > 95%. The same sequence applied to both diastereomeric intermediate N-acyl derivatives furnishes the full set of four N-Boc β-CF₃-α-prolines in only three synthetic steps, without the need for chiral chromatography. This robust resolution protocol transforms β-CF₃-α-proline ester into a easily accessible chiral building block for peptide synthesis, conformational studies and medicinal chemistry applications.