Synthesis of α- and β-N-oxalyl-l-α,β-diaminopropionic acids and their isolation from seeds of Lathyrus sativus

Phytochemistry
1977.0

Abstract

The a- and fl-N-oxalyl derivatives of La,/&diaminopropionic acid have been chemically synthesized and also isolated from seed extracts of Ladhyrus satiuus. Chemical and physical properties of the natural and synthetic isomers were in good agreement. The toxicity of the a-isomer to chicks was evaluated and compared with that of the p-isomer.The consumption of Lathyrus sativus seeds by human populations is correlated with the incidence of neurolathyrism, a chronic paralysing disease [l-3]. A number of substances acutely toxic to experimental animals have been isolated from L. satiuus seeds, including B-Noxalyl-L-a$-diaminopropionic acid [4,5] ; N-/I-n-glycopyranosyl-N-a-L-arabinosyl-a$-diaminopropionitrile [6, fl and phenolic material of unknown structure [8]. There is strong experimental evidence that fl-N-oxalyldiaminopropionic acid is the principal causative agent in neurolathyrism [9, lo], but the mechanism of action of this compound is unknown and it is uncertain whether neurolathyrism is caused by the compound alone.L. sativus seed also contains a-N-oxalyl-L-a&diaminopropionic acid [l l-133, although the quantity in fresh seed extracts is small. However, the a- and P-Noxalyl derivatives of a$-diaminopropionic acid readily interconvert and the process is accelerated by heating [l 1). Hence the a-isomer probably constitutes a significant proportion of the total quantity of N-oxalyldiaminopropionic acids in the seeds after cooking prior to human consumption. Similarly, isomerization could occur in uioo following ingestion of the b-isomer. It is not known whether the a-isomer is chronically toxic to animals, and such information is essential for a full understanding of the toxicity of L. satious seed. A recent report [14] suggests that the a-isomer is not acutely toxic to l-dayold chicks or to neonatal mice.Progress in elucidating the mechanism of action of fi-N-oxalyldiaminopropionic acid has been hampered by the unavailability of the compound in a pure form. Earlier synthesis gave very poor yields [4, 151, but a successful synthesis was reported by Rao [16]. A synthetic route to the a-isomer was recently described [14]. This paper reports alternative syntheses of the individual a- and fl-N-oxalyl derivatives of L-a&? diaminopropionic acid and a method by which the two isomers can be isolated from seed extracts of L. satious.

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