Glycine, Strecker amino acid synthesis

The preparation of the novel ligand 202b illustrates the general synthetic approach to this class of quaternary a,a-disubstituted glycine sulfonamides (Scheme 17). Menthone (203) is converted to 204 using the Strecker amino acid synthesis procedure. A short sequence of synthetic manipulations subsequently yields the desired amino acid Hgand 206. 

The importance of chemical syntheses of a-amino acids on industrial scale is limited by the fact that the standard procedure always yields the racemic mixture (except for the achiral glycine H2N-CH2-COOH and the corresponding amino acid from symmetrical ketones R-CO-R). A subsequent separation of the enantiomers then is a major cost factor. Various methods for the asymmetric synthesis of a-amino acids on laboratory scale have been developed, and among these are asymmetric Strecker syntheses as well. ... 

Glycine and the other amino acids are probably formed via the Strecker-cyano-hydrin synthesis (which has been known for more than 150 years) from aldehyde, HCN and ammonia, with subsequent hydrolysis (Strecker, 1850,1854 Miller, 1953). 

There are several laboratory-size methods for synthesizing amino acids, but few of these have been scaled up for industrial production. Glycine and m.-alanine are made by the Stnecker synthesis, commencing with formaldehyde and acetaldehyde, respectively. In tile Strecker synthesis, aldehydes react with hydrogen cyanide and excess ammonia to give amino niiriles which, in turn, are converted into a -amino adds upon hydrolysis. 

Hydrogen cyanide and methanal are especially reasonable starting materials for the prebiotic synthesis of amino acids, purine and pyrimidine bases, ribose and other sugars. Formation of glycine, for example, could have occurred by a Strecker synthesis (Section 25-6), whereby ammonia adds to methanal in the... 

An important application of oxidation of a C-H bond adjacent to a nitrogen atom is the selective oxidation of amides. This reaction proceeds in the presence of ferf-BuOOH as the oxidant and Ru(II) salts. Thus in the example of Eq. (36), the a-tert-butylperoxy amide of the isoquinoline was obtained, which is an important synthetic intermediate for natural products [138]. This product can be conveniently reacted with a nucleophile in the presence of a Lewis add. Direct trapping of the iminium ion complex by a nudeophile was achieved in the presence of trimethylsilyl cyanide, giving a-cyanated amines as shown in Eq. (37) [45]. This ruthenium/peracid oxidation reaction provides an alternative to the Strecker reaction for the synthesis of a-amino acid derivatives since they involve the same a-cyano amine intermediates. In this way N-methyl-N-(p-methoxyphenyl) glycine could be prepared from N,N-dimethyl-p-methoxyaniline in 82% yield. 

Davis and Fanelli applied the sulfinimine mediated asymmetric Strecker synthesis to the enantioselective synthesis of the racemization-prone (/ )-(4-methoxy-3,5-dihydroxyphenyl)glycine (134) from 133.81 This amino acid is the central amino acid of the clinically important glycopeptide antibiotic vancomycin as well as related antibiotics. 

Over 500 different a-amino acids have now been synthesized or isolated. About 20 of them form the main components of proteins (see also Chapter 30). a-Amino acids are commerically obtained by fermentation of glucose (arg, asp, gin, glu, his, ile, lys, pro, val, thr) or glycine (ser), or enzymatic attack on aspartic acid (ala) or fumaric acid (asp), by hydrolysis, for example, of casein or sugar beet waste (arg, cys, his, hyp, leu, tyr), by transformation of ornithine (arg) or glutamic acid (gin), or, alternatively, by complete synthesis from aldehydes using the Strecker synthesis (ala, gly, leu, met, phe, thr, trp, val), from acrylonitrile (gly, lys), or from caprolactam (lys). The racemates are obtained by total synthesis, but L-amino acids are produced by all the other processes. The racemates are separated and the D-isomers produced are again racemized. 

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