Pyrrolines pyrroline-5-carboxylate

The reactivity of the methylene group adjacent to the lactam group affords the possibility of a Claisen condensation. Thus, treatment of 2-pyrrolidone or 2-piperidone with ethyl oxalate leads to the J -pyrroline-carboxylic (70) and, d -piperideine-2-carboxylic acids (71), respectively. N-methyl lactams furnish N-methyl derivatives (72,73) (Scheme 3). 

VII. Enzymic Formation of Pyrroline Carboxylic Acid from... 

Potassium tert-butanol Pyrrole-2-carboxylic acid esters from tosylglycine esters via 3-hydroxypyrrolidine- and J -pyrroline-carboxylic acid esters... 

Pro is glucogenic. It does not participate in a-helix formation, and therefore has spedal importance in protein tertiary structure (see oteins). Pro is biosynthesized chiefly from L-glutamate via glutamic-y-semialdehyde. Some may ako be formed from exogenous ornithine via pyrroline carboxylic add. It is a nonessential amino add in mammals, but is essential for Ae growA of chickens AzetiAne-2-carboxylic acid is a Pro antagonist. 

There is a. ccTtain amount of evi(l(Mic( that tlu semialdehydo of glutamic acid is the intermediate formy the loss of the 5-araino group of ornithine. This evidence is the isolation of what was presumed to be the 2,4-dinitrophenylhydrazone of the semialdehyde upon partial oxidation of proline by the cyclophorase system. The glutamic acid semialdehyde can be expected to condense readily to pyrroline carboxylic acid, and reduction of this compound would yield proline (Fig. 2). 

The same mitochondrial extracts also catalyzed the formation from proline of a carbonyl compound which reacts positively with 0-amino-benzaldehyde. This is a test for pyrroline carboxylate compounds. Unexpectedly, this oxidation reaction proceeded anaerobically. 

The conversion of ornithine to A -pyrroline -carboxylate is better understood, since the transamination reaction by which this occurs has been studied in some detail with Neurospora 121) and liver extracts 122). The equilibrium of the transaminase reaction with a-ketoglutaric acid as amino group acceptor favors A -pyrroline-5-carboxylate formation about 90% of the ornithine is decomposed. 

It is interesting to note that 4-aminopent-3-en-2-one (85), which is held in a cisoid arrangement by hydrogen bonding, gives the product 86, which is stable in anhydrous solvent, but which cyclizes under the influence of water to give methyl 2-methyl-5-oxo-4-(2-oxopropylidene)-2-pyrroline-3-carboxylate (87). 

By use of potassium phthalimide we can isolate the intermediate. a-Oxo-S-aminovaleric (9, = 1) and a-oxo-e-aminocaproic acids (9, = 2) readily yield 2l -pyrroline-2-carboxylic acid (10, =1) and. d -piperideine-2-carboxylic acids (10, n = 2), respectively (7-10). The equilibria of the acids with their cyclic forms was observed in water solutions (11,12). 

Condensation of -pyrroline with pyrrole readily affords 2-(2-pyrro-lidyl)pyrrole (82). The dimerizations of some derivatives of A -piperideine, e.g., zl -pyrroiine and -piperideine-2-carboxylic acids, take a similar course (301). 

FIGURE 16.7 The proline racemase reaction. Pyrrole-2-carboxylate and A-l-pyrroline-2-carboxylate mimic the planar transition state of the reaction. 

There is no associated impairment of hydroxyprohne catabolism. The metabolic block in type II hyperpro-linemia is at glutamate-7-semiaIdeliyde dehydrogenase, which also functions in hydroxyprohne catabolism. Both proline and hydroxyprohne catabohsm thus are affected and A -pyrroline-3-hydroxy-5-carboxylate (see Figure 30-10) is excreted. 

Muramatsu H, H Mihara, R Kakutani, M Yasuda, M Ueda, T Kurihara, N Esaki (2005) The putative malate/ lactate dehydrogenase from Pseudomonas putida is an NADPH-dependent ALpiperideine-2-carboxyl-ate/A -pyrroline-2-carboxylate reductase involved in the catabolism of L-lysine and D-proline. J Biol Chem 280 5329-5335. 

Dipolar cycloadditions of 2-tert-butoxycarbonyl-1 -pyrroline A -oxide (627) with several chiral acrylamides (634a-f) (Scheme 2.276) followed by hydrogenolysis of cycloadducts (635) and (636) has been used in the synthesis of enantiopure tert-butyl (2RJ R)- and (2.S. 7a.S )-2-hydroxy-3-oxo-tetrahydro-l II -pyrrolizine-7a(5// )-carboxylates, useful intermediates for the synthesis of Gly-(s-cis)Pro dipeptide mimetic (790). 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Proline is oxidised to form pyrroline-5-carboxylate, and FAD is the hydrogen acceptor. The pyrroline-5-carboxyl-ate is converted, via several reactions, to glntamate ... 

Additional communications deal with the synthesis of pyrrolo[l,2-cjquinazolines by treatment of methyl 3-alkyl-l,3-dihydro-2-oxo-3-(triphenylphosphoranylidenamino)-2//-indole-l-carboxylates (275) with ketones to afford A -pyrrolin-4-ones (276). As Scheme 100 shows, 276 can... 

Maleylacetoacetate Fumarylacetoacetate Acetoacetate ( Glutamate 4-semialdehyde A -Pyrroline-5-carboxylate... 

This enzyme [EC 1.4.1.12] catalyzes the reaction of 2,4-diaminopentanoate with NAD(P)+ and water to produce 2-amino-4-oxopentanoate, ammonia, and NAD(P)H. The enzyme can also utilize 2,5-diaminohexanoate as a substrate (although not as effectively as the substrate mentioned above) forming 2-amino-5-oxohexanoate, which then cyclizes nonenzymically to form 1-pyrroline-2-methyl-5-carboxylate. 

This enzyme [EC 1.5.1.12] catalyzes the reaction of 1-pyrroline-5-carboxylate with NAD+ and water to produce L-glutamate and NADH. The enzyme will also act on 3-hydroxy-l-pyrroline-5-carboxylate to generate 4-hy dr oxy glutamate. 

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