Gamma-fluorinated analogues of glutamic acid and glutamine.
Gamma-fluorinated analogues of glutamic acid and glutamine are compounds of biological interest. Syntheses of such compounds are extensively reviewed in this article. 4-fluoroglutamic acid was prepared as a mixture of racemic diastereomers by Michael reaction, inverse-Michael reaction or by electrophilic / nucleophilic fluorination. Optically enriched 4-fluoroglutamic acids were obtained by several resolution techniques as well as by asymmetric methodologies using the chiral pool. 4-fluoroglutamine was prepared as a mixture of stereoisomers as well as in racemic erythro and threo forms from the corresponding 4-fluoroglutamic acids using aminolysis and conventional protection and deprotection strategies. Racemic 4,4-difluoroglutamic acid was synthesized by a nitroaldol reaction and its L-enantiomer obtained via three different asymmetric routes. Racemic 4,4-difluoroglutamic acid was converted into the corresponding 4,4-difluoroglutamine using a protection / aminolysis / deprotection sequence while N-Boc-L-4,4-difluoroglutamine was prepared directly from (R)-Garner's aldehyde using a Reformatsky reaction as the key step.
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UMR 7573-C.N.R.S., ENSCP, 11 rue Pierre et Marie Curie, F-75231 Paris Cedex 05, France.
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D005461:Fluorine / Q000737:chemistry*; D018698:Glutamic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D005973:Glutamine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D013237:Stereoisomerism
D005973:Glutamine; D005461:Fluorine; D018698:Glutamic Acid