TY - JOUR
T1 - (2R,3S)-3,4,4,4-Tetrafluorovaline
T2 - A Fluorinated Bioisostere of Isoleucine
AU - Brewitz, Lennart
AU - Noda, Hidetoshi
AU - Kumagai, Naoya
AU - Shibasaki, Masakatsu
N1 - Funding Information:
This work was financially supported by ACT-C (JPMJCR12YO) from JST, and KAKENHI (17H03025 and JP18H04276 in Precisely Designed Catalysts with Customized Scaffolding) from JSPS and MEXT. Dr. Ryuichi Sawa and Dr. Kiyoko Iijima are gratefully acknowledged for assistance in obtaining HRMS spectra. Dr. Tomoyuki Kimura is gratefully acknowledged for assistance in X-ray crystallography.
Funding Information:
This work was financially supported by ACT‐C (JPMJCR12YO) from JST, and KAKENHI (17H03025 and JP18H04276 in Precisely Designed Catalysts with Customized Scaffolding) from JSPS and MEXT. Dr. Ryuichi Sawa and Dr. Kiyoko Iijima are gratefully acknowledged for assistance in obtaining HRMS spectra. Dr. Tomoyuki Kimura is gratefully acknowledged for assistance in X‐ray crystallography.
Publisher Copyright:
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/3/22
Y1 - 2020/3/22
N2 - The synthesis of (2R,3S)-3,4,4,4-tetrafluorovaline, a fluorinated derivative of the canonical α-amino acid l-valine, is reported for the first time. A highly enantio- and diastereoselective direct catalytic asymmetric Mannich-type reaction was applied as the key C–C bond-forming step to afford gram quantities of a central synthetic intermediate. The conformation of the novel fluorinated α-amino acid was analyzed by X-ray crystallography, NMR spectroscopy, and computational methods, which, together with its calculated and experimental physicochemical properties, indicated that the fluorinated valine is a bioisostere of l-isoleucine.
AB - The synthesis of (2R,3S)-3,4,4,4-tetrafluorovaline, a fluorinated derivative of the canonical α-amino acid l-valine, is reported for the first time. A highly enantio- and diastereoselective direct catalytic asymmetric Mannich-type reaction was applied as the key C–C bond-forming step to afford gram quantities of a central synthetic intermediate. The conformation of the novel fluorinated α-amino acid was analyzed by X-ray crystallography, NMR spectroscopy, and computational methods, which, together with its calculated and experimental physicochemical properties, indicated that the fluorinated valine is a bioisostere of l-isoleucine.
KW - Bioisosterism
KW - Conformational analysis
KW - Cooperative catalysis
KW - Fluorinated amino acid
KW - Physicochemical properties
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U2 - 10.1002/ejoc.202000109
DO - 10.1002/ejoc.202000109
M3 - Article
AN - SCOPUS:85082126567
VL - 2020
SP - 1745
EP - 1752
JO - Justus Liebigs Annalen der Chemie
JF - Justus Liebigs Annalen der Chemie
SN - 0365-5490
IS - 11
ER -