IDENTIFICATION OF THE ELUSIVE AMINO ACID 3 fe 6 
ESTABLISHMENT OF STRUCTURE VIA SYNTHESIS AND RESOLUTION 
Although degradative methods may serve to identify the structure of a new natural 
amino acid with a fair degree of reliability, the structure can by no means be con- 
sidered as having been unequivocally established until the material has been obtained 
by synthesis and subsequent resolution, and the physical, chemical and biological 
NH»—-CH-CO2H NH2-CH-CO2H 
CH HO-CCOpH 
HO-CH-CO>H CH3 
y—Hydroxyglutamic Acid [B—-Hydroxy——methylaspartic Acid 
HI 
NH2—CH—CO2H NH2—-CH—CO2H NH2—CH—CO2H 
CH2 CO2H CHCO2H CHCO2H 
CHa CHCOzH 
Aspartic Acid —Methylaspartic Acid a—Aminotricarballylic Acid 
NH> 
MPG oh —CH,CHCO,H 
(CH), 
NH>-CH-COoH apace 
a,e-Diaminopimelic Acid NH 
Cystine 
Fig. 3 Structures of mono- and diaminopolycarboxylic acids as related to CO, liberation with 
ninhydrin. 
properties of the synthetic and natural products proven identical. Several of the 
more general methods employed for the synthesis of amino acids include: (a) the 
Strecker synthesis; (b) amination of a-halogen acids; (c) reductive amination; (d) 
amination via molecular rearrangement; (e) condensation of an aldehyde with an 
active methylene group; and (f) condensations with N-substituted aminomalonic 
esters (cf. ref. 37). Probably the most versatile of the presently available methods is 
the last-mentioned procedure, which involves the sodium ethoxide-mediated con- 
densation either of acetylaminomalonic ester (I; R = CH,) or ethyl acetamido- 
cyanoacetate (V; R = CH,), both of which are commercially available, with a suitable 
CO,Et CO,Et R’ CN CN 
R’Br | | | R’Bx | 
CHNH—COR —-> C(R’)NH—COR —> CHNH, <— C(R’)NH—COR <-— CHNH—COR 
| | | 
CO,Et CO,Et CO,H CO,Et CO,Et 
I iat UI IV V 
alkyl or acyl halide (R’Br). Acid hydrolysis of the pertinent condensation product 
(II or IV) then yields the desired amino acid (III). 
The synthetic procedures listed above may be considered as general only insofar 
as the assumption is valid that the requisite starting materials are available. Such is 
not invariably the case, however, for the side chains of amino acids are possessed of 
a most diverse structure and may require the expenditure of considerable effort for 
References p. 22/24 
