A-Amino acid synthesis

These two methods ate popular for a-amino acid synthesis, and used in the industrial production of some amino acids since taw materials are readily available. 

Alkylation of protected glycine derivatives is one method of a-amino acid synthesis (75). Asymmetric synthesis of a D-cx-amino acid from a protected glycine derivative by using a phase-transfer catalyst derived from the cinchona alkaloids (8) has been reported (76). 

Asymmetric Synthesis of N-tert-Butoxycarbonyl a-Amino Acids Synthesis... 

Asymmetric Synthesis of N-tert-Butoxycarbonyl a-Amino Acids Synthesis of (5S,6R)- and (5R,6S)-4-tert-Butoxycarbonyl-2,3-diphenylmorpholin-6-one. 

In particular, it is not only the cinchona alkaloids that are suitable chiral sources for asymmetric organocatalysis [6], but also the corresponding ammonium salts. Indeed, the latter are particularly useful for chiral PTCs because (1) both pseudo enantiomers of the starting amines are inexpensive and available commercially (2) various quaternary ammonium salts can be easily prepared by the use of alkyl halides in a single step and (3) the olefin and hydroxyl functions are beneficial for further modification of the catalyst. In this chapter, the details of recent progress on asymmetric phase-transfer catalysis are described, with special focus on cinchona-derived ammonium salts, except for asymmetric alkylation in a-amino acid synthesis. 

In cases where the natural amino acid side chains of enzymes are insufficient to carry out a desired reaction, the enzyme frequently uses coenzymes. A coenzyme is bound by the enzyme along with the substrate, and the enzyme catalyses the bimolecular reaction between the coenzyme and the substrate (cf. Section 2.6.3). A simple model for a-amino acid synthesis by transamination was developed by substituting /I-cyclodextrin with pyridoxamine. Pyridoxamine is able to carry out the transformation of a-keto acids to a-amino acids even without the presence of the cyclodextrin, but with the cyclodextrin cavity as well, the enzyme model proves to be more selective and transaminates substrates with aryl rings bound strongly by the cyclodextrin much more rapidly than those having little affinity for the cyclodextrin. Thus (p-le/f-butylphenyl) pyruvic acid and phenylpyruvic acid are transaminated respectively 15 000 and 100 times faster then pyruvic acid itself, to give (p-le/f-butylphenyl) alanine and phenylalanine (Scheme 12.5). 

Diethyl acetamidomalonate, CH3C0NHCH(C02Et)2 Reacts with alkyl halides in a common method of a-amino acid synthesis (Section 26.3). 

For recent developments in the area of a-amino acid synthesis, see O Donnell, M. J., Ed. Symposia-in-Print , Tetrahedron 1988, 44, 5253-5614. 

In its utilization of acetonitrile, the oxazoline synthesis shown in Scheme 56 resembles a Ritter reaction.The procedure is convenient, but yields are variable the pyrolysis gives starting alkene plus acetamide as by-products. Another oxazoline synthesis and subsequent conversion to a cif-amino alcohol is discussed later (Scheme 85). A recent y-hydroxy-a-amino acid synthesis incorporates the following type of transformation (Scheme 57).If a three-day equilibration with anhydrous HBr was introduced iMtween stages i and ii, almost pure trans product was obtained. The paper has many usefol references. Yet another modified Ritter reaction is shown in Scheme 58. ... 

In this case the enantiomers are available by the analogous conversion of glycine r-butyl ester using Chlorofri -cyclopentadienyl)[(4R,trans)-2, 2-dimethyl-a, a, a, a -tetra-phenyl-L3-dioxolane-4,5-dimethanolato(2—)-0, 0 Jtitanium. An elegant alternative is the enantioselective addition of iso-cyanoacetate to aldehydes under the catalysis of a chiral Au complex. Further methods, also for the anti erythrd) epimers, can be found in recent reviews of enantioselective a-amino acid synthesis. ... 

ASYMMETRIC SYNTHESIS OF N-tert-BUTOXYCARBONYL a-AMINO ACIDS. SYNTHESIS OF (5S,6R)-4-tert-BUTOXYCARBONYL-5,6-DIPHENYLMORPHOLIN-2-ONE... 

Savage, I., Thomas, E. J. Asymmetric a-amino acid synthesis synthesis of (+)-polyoxamic acid using a [3,3]allylic trifluoroacetimidate rearrangement. J. Chem. Soc., Chem. Common. 1989, 717-719. 

Smith, B. (1995) Methods of Non-a-Amino Acid Synthesis, Dekker, New York. 

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