- A practical chemoenzymatic synthesis of (R)-isovaline based on the asymmetric hydrolysis of 2-ethyl-2-methyl-malonamide
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(R)-Isovaline has potential applications in drug development, and therefore the development of an efficient method for the production of (R)-isovaline is desired. Herein we have investigated the asymmetric hydrolysis of 2-ethyl-2-methyl-malonamide into (S)-2-ethyl-2-methyl-malonamic acid, a useful synthetic intermediate in the production of (R)-isovaline, using CsAM, which is a recombinant amidase originally derived from Cupriavidus sp. KNK-J915. The produced (S)-2-ethyl-2-methyl-malonamic acid (98.6% ee) could be easily converted into (R)-isovaline by the Hofmann rearrangement. Starting from diethyl 2-methylmalonate, we obtained (R)-isovaline (99.1% ee) in 58.6% yield over eight steps, including the CsAM-catalyzed asymmetric hydrolysis of 2-ethyl-2-methyl-malonamide.
- Nojiri, Masutoshi,Yoshida, Fumi,Hirai, Yoshinori,Nishiyama, Akira,Yasohara, Yoshihiko
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- Preparation and synthetic applications of (S)- and (R)-N-boc-N, O- isopropylidene-α-methylserinals: Asymmetric synthesis of (S)- and (R)-2- amino-2-methylbutanoic acids (Iva)
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This report describes an efficient and convenient large-scale synthesis procedure for (S)- and (R)-N-Boc-α-methylserinal acetonides (3 and 4) starting from (R)-2-methylglycidol 5. The application of both of these compounds as valuable chiral building blocks in the asymmetric synthesis of α-methylamino acids is also demonstrated by the synthesis of (S)- and (R)- isovalines (Iva) (6 and 7).
- Avenoza, Alberto,Cativiela, Carlos,Corzana, Francisco,Peregrina, Jesus M.,Zurbano, Maria M.
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p. 8220 - 8225
(2007/10/03)
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- Asymmetric Synthesis of α-Substituted Amino Acids and Amines by Carbon-Carbon Bond Formation in Position α to the Nitrogen
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The asymmetric synthesis of α-substituted α-amino acids and propargylamines is described.As chiral auxiliary we used (S)-(-)-1-dimethoxymethyl-2-methoxymethylpyrrolidine (SDMP, 1).Treatment of the amino acids or amines with SDMP 1 afforded the correspondi
- Kolb, Michael,Barth, Jacqueline
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p. 1668 - 1688
(2007/10/02)
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