Fluoroglutamic acid

Hudlicky, M. Merola, J.S. New stereospecific synthesis and X-ray diffraction structures of (—)-D-erythro- and (-I- )-L-threo-4-fluoroglutamic acid. Tetrahedron Lett. 1990, 31, 7403-7406. 

Konas, D.W. Coward, J.K. Electrophilic fluorination of pyroglutamic acid derivatives application of substrate-dependent reactivity and diastereoselectivity to the synthesis of optically active 4-fluoroglutamic acids. J. Org. Chem. 2001, 66, 8831-8842. 

Transformation using glutamate dehydrogenase is an elegant approach to (2R,3R)- and (2.R,3S)-3-fluoroglutamic acid 76 [69]. 

DAST was used to prepare important / -fluoroamino acids from the corresponding hydroxy derivatives1611 including fluoroglutamic acid (15) (equation 90)161 and fluorodiaminopimelic acid, a potent inhibitor to enzymes found in Escherichia coli162. 

Compound (VIII.98), a folic acid analogue with a y-fluoro substituent in the side-chain was described first by Alekseeva e/ al. [281] and several years later by Bergmann and Chun-Hsu [282]. The synthesis of (VIII.98), as mixture of threo and erythro isomers, was achieved via the Waller method from V-(4-ami-nobenzoyl)-y-fluoroglutamic acid, 2,4,5-triamino-6(lif)-pyrimidinone, and 2,3-dibromopropionaldehyde, but the yield was low (5.6%). y-Fluoroglutamic acid, as a mixture of D- and L-enantiomers, was prepared from diethyl 2-fluoromalonate by condensation with ethyl 2-acetamidoacrylate followed by hydrolysis and decarboxylation in refluxing 12 M HCl, or from ethyl 3-chloro-2-hydroxypropanoate by a sequence consisting of (i) 0-t-butylation with CH2 = C(CH3)2, (ii) condensation with diethyl 2-acetamidomalonate, (hi)... 

In the later work, Coward and coworkers carried out a study of electrophilic fluorination of pyroglutamic acid derivatives. The results provided an alternative route to fluorinated pyroglutamic acids and derived fluoroglutamic acids." " Conditions were found that led to diastereoselective monofluorination to produce 40, but attempts to carry out difluorination of the substrate were unsuccessful. The bicyclic... 

FIGURE 3.18 Fluorinated pyroglutamic acid as a precursor of fluoroglutamic acid. 

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