1H NMR study of protected and unprotected kainoid amino acids: facile assignment of C-4 stereochemistry.
The kainoid amino acids exhibit potent neuroexcitatory activity in the mammalian central nervous system. Around their pyrrolidine ring, a trans disposition between the C-2 and C-3 substituents and a cis relationship between the C-3 and C-4 substituents are crucial for their potent biological activity. During synthetic studies into the kainoids, we have established a straightforward, empirical rule, which allows the facile assignment of C-4 stereochemistry to both protected and unprotected kainoids. When pairs of C-4 epimers are available, the rule indicates that, when their (1)H NMR spectra are compared, one of the methylene protons on the C-3 side chain appears at significantly lower chemical shift in the C-3, C-4 cis isomer than the corresponding signal for the proton in the spectrum for the C-3, C-4 trans isomer. In addition, the rule states that the difference in chemical shift between the two individual protons on the C-3 side chain of the C-3, C-4 cis isomer is significantly greater than the corresponding difference for the C-3, C-4 trans isomer. The rule is demonstrated for kainoids possessing an unsaturated substituent at C-4 and when comparing spectra in D(2)O for pairs of unprotected C-4 epimers, the spectra were recorded at approximately the same pD.
Baldwin
J E
JE
The Dyson Perrins Laboratory, South Parks Road, Oxford OX1 3QY, U.K. jack.baldwin@chem.ox.ac.uk
Fryer
A M
AM
Pritchard
G J
GJ
D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000737:chemistry; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry; D006801:Humans; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011522:Protons; D013237:Stereoisomerism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011522:Protons; D007608:Kainic Acid