2-Allylglycine

R5-a-Allylglycine (2-aminopent-4-enoic acid). [7685-44-1] M 115.1, m 250-255"(dec), pKesi(I) 2.3, pKesi(2) 9.6. Dissolve in absolute EtOH and ppte with pyridine, then recrystallise from aqueous EtOH [Rp in Bu0H Et0H NH3 H20 (4 4 1 ) 0.37]. The hydrobromide has m 136-140° (from EtOAc) and the phenylureido derivative has m 159-161°. [Monatsh Chem 89 377 1958.]... 

Reducing the availability of GABA by blocking the synthesising enzyme GAD also promotes convulsions. This may be achieved by substrate competition (e.g. 3-mercapto propionic acid), irreversible inhibition (e.g. allylglycine) or reducing the action or availability of its co-factor pyridoxal phosphate (e.g. various hydrazides such as semi-carbazide). In fact pyridoxal phosphate deficiency has been shown to be the cause of convulsions in children. 

The addition of perfluoroalkyl iodides to simple olefins has been quite successful under aqueous conditions to synthesize fluorinated hydrocarbons.119 In addition to carbon-based radicals, other radicals such as sulfur-based radicals, generated from RSH-type precursors (R = alkyl, acyl) with AIBN, also smoothly add to a-allylglycines protected at none, one, or both of the amino acid functions (NH2 and/or CO2H). Optimal results were obtained when both the unsaturated amino... 

Hanessian reported the synthesis of enantiomerically pure or highly enriched allylglycine and its chain-substituted analogs from the reaction of the sultam derivatives of O-benzyl glyoxylic acid oxime with ally he bromides in the presence of zinc powder in aqueous ammonium chloride (Eq. 11.41).72 Brown noticed the critical importance of water in the asymmetric allylboration of /V-trimethylsilyIbcnzaldimines with B-allyldiisopinocampheylborane.73 The reaction required one equivalent of water to proceed (Eq. 11.42). 

The X-ray structure of [cp Ir(CNR)Cl2], CNR = l,3,4,6-tetra-0-acetyl-2-deoxy-2-isocyano-Q,, 3-D-glucosc, has been determined.428 The synthesis of chiral complexes of Ir111 with Q-amino acid anions, L-L, of general formula [cp Ir(Cl)(L-L )] (252), and their NMR spectroscopic characterization, have been detailed. The X-ray structures of (252), L-L = L-proline and [cp Ir(Cl)(L-His-OH)]Cl, His = histidine, are described.429 C-allylglycinate binds in a terdentate manner in (253), which has been characterized by X-ray diffraction studies.430 C-vinylglycinate forms complex (254). 

Although the metathesis reaction with allylglycine 23 did not go to completion, a moderate yield of the desired cross-metathesis product was isolated. Very recently, Blechert has reported two similar cross-metathesis reactions of an allylglycine 25 using the ruthenium catalyst [44]. In these cases higher yields of the cross-metathesis products were isolated, presumably due to the higher reaction temperatures employed (Eq. 26). 

When a sample of phenylalanine carrying a 14C label in the benzene ring was photolysed at 254 nm, it gave radioactive 2-allylglycine (2-aminopent-4-enoic acid, 16). This showed that the irradiation had disrupted the aromatic ring [23],... 

Asymmetric Synthesis of a-Amino Acids by the Alkylation of Pseudoephedrine Glycinamide. Preparation of L-Allylglycine and N-Boc L-Allylglycine. 

Macrocyclization of esters of allylglycine with diols has been successfully used to prepare derivatives of 2,7-diaminosuberic acid [861,864]. The latter are surrogates of cystine, and therefore of interest for the preparation of peptide mimetics. For unknown reasons protected allylglycine derivatives can not be directly dimerized by self metathesis [864]. However, catechol [864], ethylene glycol [861], and 1,2- or 1,3-di(hydroxymethyl)benzene derivatives [860] of allylglycine are suitable templates for the formal self metathesis of this amino acid via RCM. 

In a multistep reaction sequence, A-Boc-L-allylglycine was converted into detoxinine 9 (84TL4133). Hydroxymethyl L-allylglycine was converted via a lactone into (-)-bulgenicine 10 (86TL6079). 

GABA synthesis inhibitors act on the enzymes involved in the decarboxylation and transamination of GABA. Glutamic acid decarboxylase (GAD), the first enzyme in GABA biosynthesis, is inhibited easily by carbonyl reagents such as hydrazines [e.g., hydrazinopropionic acid (4.164) or isonicotinic acid hydrazide (4.165)], which trap pyridoxal, the essential cofactor of the enzyme. A more specific inhibitor is allylglycine (4.166). All of these compounds cause seizures and convulsions because they decrease the concentration of GABA. 

Allyl bromide 1-Propene, 3-bromo- (106-95-6), 76, 60, 221 Allyl chloride 1-Propene, 3-chloro- (107-05-1), 77, 254 l ALLYLGLYCINE 4-PENTENOIC ACID, 2-AMINO-, (R)- (54594-06-8), 76, 57 Allylic alcohols, enantioselective cyclopropanation, 76, 97 ALLYLINDATION, 77, 107... 

Cross-metathesis enables the efficient preparation of acyclic alkenes and 1,3-dienes on insoluble supports (Figure 5.16). Unfortunately, some types of substrate show a high tendency to yield products of self-metathesis, i.e. symmetrical internal alkenes produced by dimerization of the resin-bound alkene. This is the case, for instance, with allylglycine and homoallylglycine derivatives. Dimerization of the resin-bound alkene can, however, be effectively suppressed by reducing the loading of the support [127]. 

Whilst the use of Taddol as an asymmetric phase-transfer catalyst for asymmetric Michael reactions was only moderately successful, it was much more enantioselec-tive in catalyzing alkylation reactions. For this study, Belokon and Kagan employed alanine derivatives lib and 16a-c as substrates, and investigated their alkylation with benzyl bromide under solid-liquid phase-transfer conditions in the presence of 10 mol % of Taddol to form a-methyl phenylalanine, as shown in Scheme 8.8. The best results were obtained using the isopropyl ester of N-benzylidene alanine 16b as substrate and sodium hydroxide as the base. Under these conditions, (R)-a-methyl phenylalanine 17 could be obtained in 81% yield and with 82% ee [19]. Under the same reaction conditions, substrate 16b reacted with allyl bromide to give (R)-Dimethyl allylglycine in 89% yield and with 69% ee, and with (l-naphthyl)methyl chloride to give (R)-a-methyl (l-naphthyl)alanine in 86% yield and with 71% ee [20]. 

This approach to N-alkynylsulfonamides has been applied to the synthesis of enantiomerically pure derivatives 27 of N-(ethynyl)allylglycine (Scheme 52) [152]. In this case, deprotonated sulfonamide derivatives of (S)-allylglycine were treated with ethynyl(phenyl)iodonium triflate (28), since the trimethylsi-lylethynyl salt 26 was not very effective for this purpose. 

The reaction can be applied to imines. Recently, the preparation of chiral allylglycines was effected by addition of allyl groups to the C=N bond in glyoxylic acid oximes modified as chiral sultams (Oppolzer chiral induction methodology).55 The yields (> 88%) and the diastereoselectivity (d.e. > 80 20) are excellent. 

FIGURE 13.6 Functional allylglycine derivatives prepared through hydrogenation. 

Substituted pipecolic acid derivatives can be accessed from a suitably protected allylglycine derivative by first use of a palladium-catalyzed N, O-acetal formation followed by RCM.43 Treatment of 19 with boron trifluoride etherate followed by a variety of nucleophiles formed the corresponding substituted products 20 and 21 (Scheme 28.12). 

Meldrum, B. S., Horton, R. W., Brierley, J. B. (1974). Epileptic brain damage in adolescent baboons following seizures induced by allylglycine. Brain, 97, 407-418. 

Once the strategy was selected, the validation of the relevant cyclization in solution and the determination of its stereochemical outcome and yield were carried out. The synthetic scheme is reported in Fig. 3.6. The commercially available allyl (3.3) and propargylglycines (3.7) were sequentially tosylated and alkylated with propargyl and allyl bromide, respectively, to give 3.5 and 3.9. The intramolecular Pauson-Khand cyclization produced the two isomers 3.6 and 3.10, with different stereochemistries, in a stereospecific reaction (the chiral allylglycine produced 3.6 as a single enantiomer. 

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