131690-61-4Relevant articles and documents
-
Richtmyer
, p. 1137 (1946)
-
Substrate-controlled Diastereoselective Michael Addition of Alkylidene Malonates by Grignard Reagents
Zhou, Wei,Xiao, Qingwei,Chang, Yuanyuan,Liu, Qifa,Zang, Xiaohao,Hu, Mengmeng,Zeng, Xi,Du, Zhiyun,Zhong, Guifa
, p. 116 - 121 (2019/12/14)
Herein is described a diastereoselective Michael addition of Grignard reagents to a, b- unsaturated diethyl malonates incorporated with a 2-oxazolidone chiral auxiliary. The catalyst-free Michael addition proceeds with good chemical efficiency and excellent stereoselectivity; and it provides new thoughts to the asymmetric synthesis of b-substituted b3 amino acid derivatives. Optically active b-amino acid derivatives are commonly found in various biologically active compounds from natural sources and organic synthesis.1, 2 They have been also widely adopted as building blocks for the construction of a/b-peptide foldamers which can mimic biological function of natural a-peptide of enzymes, and are less susceptible to protease degradation than the latter ones.3-7 Therefore, the development of synthetic procedures to prepare b-amino acids is a relevant endeavor. The synthesis of b-amino acids in enantiomerically pure forms continues to attract interest.8-14 The chirality conformation of b-amino acids is generally originated from chiral starting materials, chiral auxiliaries or chiral catalysts. Many approaches were developed for the preparation of substituted b-amino acids, such as hydrogenation of enamines catalyzed by rhodium or palladium with chiral phosphepine ligands15, 16, addition of aromatic amines to a-b unsaturated imides catalyzed by palladium complex17, thiourea catalyzed asymmetric Mannich reaction18 and chiral amine catalysed aza-Michael addition19-22. Although various methods for the synthesis of substituted b-amino acids have been developed with good yield and stereoselectivity, arduous availability of chiral catalysts is still an unavoidable obstacle for the wide use of these methods. Thus, it is still desirable to develop novel catalyst-free strategies to construct these privileged skeletons. The use of chiral auxiliaries is another important strategy to synthesize of b-amino acids. In this context, Goodman et al. reported pseudoephedrine as a chiral auxiliary for the synthesis of a-substituted b-amino acids23. Juaristi et al. accomplished diastereoselective synthesis of b-amino acids using hexahydrobenzoxazolidinones3. These methods provided practical approaches for the synthesis of a-substituted b-amino acids (b2-amino acids). But for b-substituted b-amino acids (b3-amino acids), it is still challenging.
Characterization of a new nitrilase from Hoeflea phototrophica DFL-43 for a two-step one-pot synthesis of (S)-β-amino acids
Zhang, Zhi-Jun,Cai, Rui-Feng,Xu, Jian-He
, p. 6047 - 6056 (2018/05/15)
A nitrilase from Hoeflea phototrophica DFL-43 (HpN) demonstrating excellent catalytic activity towards benzoylacetonitrile was identified from a nitrilase tool-box, which was developed previously in our laboratory for (R)-o-chloromandelic acid synthesis from o-chloromandelonitrile. The HpN was overexpressed in Escherichia coli BL21 (DE3), purified to homogeneity by nickel column affinity chromatography, and its biochemical properties were studied. The HpN was very stable at 30–40?°C, and highly active over a wide range of pH values (pH 6.0–10.0). In addition, the HpN could tolerate against several hydrophilic organic solvents. Steady-state kinetics indicated that HpN was highly active towards benzoylacetonitrile, giving a KM of 4.2?mM and a kcat of 170?s?1, the latter of which is ca. fivefold higher than the highest record reported so far. A cascade reaction for the synthesis of optically pure (S)-β-phenylalanine from benzoylacetonitrile was developed by coupling HpN with an ω-transaminase from Polaromonas sp. JS666 in toluene-water biphasic reaction system using β-alanine as an amino donor. Various (S)-β-amino acids could be produced from benzoylacetonitrile derivatives with moderate to high conversions (73–99%) and excellent enantioselectivity (> 99% ee). These results are significantly advantageous over previous studies, indicating a great potential of this cascade reaction for the practical synthesis of (S)-β-phenylalanine in the future.
