111248-06-7Relevant academic research and scientific papers
Enantioselective, chromatography-free synthesis of β3-Amino acids with natural and unnatural side chains
Gerfaud, Thibaud,Chiang, Ying-Ling,Kreituss, Imants,Russak, Justin A.,Bode, Jeffrey W.
scheme or table, p. 687 - 696 (2012/07/13)
β3-Amino acids are key components of some pharmaceuticals, excellent surrogates for metabolically labile α-amino acids, and building blocks for chiral heterocycles. Unfortunately they are not easily accessible in enantiomerically pure form, especially when possessing unnatural side chains. A flexible, chromatography-free process for the synthesis of enantiopure β3-amino acids possessing natural and unnatural side chains is described. The procedure uses inexpensive starting materials and reagents and offers a good alternative to the hazardous and expensive Arndt-Eistert homologation of enantiopure α-amino acids. Its utility has been demonstrated with the preparative scale synthesis of two valuable β3-amino acids possessing unnatural side chains.
Enantioselective Synthesis of 2-Alkyl-5-methylene-1,3-dioxolan-4-ones and Exo-Selective Diels-Alder Reactions with Cyclopentadiene
Roush, William R.,Brown, Bradley B.
, p. 3380 - 3387 (2007/10/02)
Highly stereoselective syntheses of chiral dienophiles (R)-1 and (R)-2 are described.Diazotization of L-serine in the presence of HCl and then treatment of the resulting β-hydroxy-α-chloropropionic acid (S)-7 with KOH provides potassium glycidate ((R)-8) in good yield and high enantiomeric purity.Treatment of (R)-8 with PhSH in MeOH then provides α-hydroxy acid (S)-10 that can be purified by recrystallization.Condensation of (S)-10 with either pivalaldehyde or cyclohexanecarboxaldehyde followed by oxidation to the sulfone and DBU-promoted elimination of benzenesulfinic acid then provides dienophiles (R)-1 and (R)-2, respectively.Highly exo-selective Diels-Alder reactions of (R)-1 and (R)-2 with cyclopentadiene are also described.The major cycloadduct (-)-15 (94percent of total) from the Diels-Alder reaction of 1 was shown to have an enantiomeric purity of 99percent ee.This figure defines the lower limit of enantiomeric purity of (R)-1.The diastereofacial selectivity of the Diels-Alder reactions of 1 in the exo manifold (50:1) is greater than that of 2 (20:1), as would be expected on the basis of the different steric requirements of the tert-butyl and cyclohexyl substituents of the two reagents.Consequently, dienophile 1 is the preferred reagent for complex synthetic applications, either as a chiral ketene equivalent or in contexts in which the α-hydroxy acid funtionality will be preserved in the ultimate synthetic target.Finally, the possible role of dipole effects on the exo selectivity of the Diels-Alder reactions of these and related dienophiles are briefly discussed.
A Formylcarbonium Ion Synthon. Synthesis of 3-Thio-Substituted 2-Amino Acids and Thio-Substituted Enamines from 2-Acyloxyacrylonitriles
Oku, Akira,Hori-ie, Naofumi,Harada, Toshiro
, p. 609 - 612 (2007/10/02)
The utilization of 2-acyloxy-3-phenylthiopropionitriles (2) which were prepared by the Michael addition of thiophenol to 2-acyloxyacrylonitriles (CH2=C(CN)OCOR), as a formylcarbonium ion synthon, was demonstrated by the transformation of 2 into S-phenylcysteine and 2-phenylthio enamines.
Laboratory-Scale Enzymatic/Chemical Syntheses of D- and L-β-Chlorolactic Acid and D- and L-Potassium Glycidate
Hirschbein, Bernard L.,Whitesides, George M.
, p. 4458 - 4460 (2007/10/02)
This paper describes preparations of D- (and L-) chlorolactic acids having enantiomeric excesses greater than 97percent by D- (and L-) lactate dehydrogenase catalyzed reduction of chloropyruvic acid with NADH.In syntheses carried out on 0.1-0.5 mol scales
