Fluorinated analogues of glutamic acid and glutamine

• Published in: Amino acids Vol. 24; no. 3; pp. 245 - 261
• Main Authors: Dave, R., Badet, B., Meffre, P.
• Format: Journal Article
• Language: English
• Published: Vienna Springer Nature B.V 01.04.2003
• Subjects: Acids
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-002-0410-9

γ-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.[PUBLICATION ABSTRACT]