Amino cyclopropane carboxylic acid

Neoefrapeptins, neoefrapeptin A Ac-Pip-Aib- Pip- Iva-Aib- Leu-/3 -Ala-Gly-Acc-Aib-Pip-Gly-Leu-Iva-aX, a group of peptides with insecticidal activity isolated from the fungus Geotrichum candidum. AU 12 neoefrapeptins (A-I, L-N) contain the very rare amino acid 1-amino-cyclopropane-carboxylic acid (Acc), and some of them (F, I, L, M) also contain (2S,3S)-3-methyl-proline instead of pipecolic acid (Pip) in position 11. Further unusual building blocks are isovaline (Iva) and the C-terminal amide moiety X = 2,3,4,6,7,8-hexahydro-l-pyrrolo [ 1,2-a]pyrimidine. Neoefrapeptins show a close sequence similarity to the efrapeptins [A. Fredenhagen et al., J. Antibiot. 2006, 59, 2006]. 

S-Adenosy I methionine, 0-,N-S- and C-methylated compounds, acetidine-2-carboxylic add, 1-amino-cycLopropane carboxylic acid, spermidine, thiamine... 

De Meijere showed that reactions of cyclopropylidene derivatives lead to amino-cyclopropane carboxylic acids via conjugate addition of an amine surrogate. Reac-... 

Amino-5-chlorobenzophenone Cyclopropane carboxylic acid chloride Phthalimidoacetyl chloride... 

Preparation of 2-Cyclopropylcarbony/amido-5-Chlorobenzophenone To 400.5 g (1.73 mols) of 2-amino-5-chlorobenzophenone dissolved in 220 g (2.18 mols) of triethylamine and 3.5 liters of tetrahydrofuran is added cautiously 181 g (1.73 mols) of cyclopropane-carboxylic acid chloride. The reaction is refluxed 2 /2 hours and allowed to cool to room temperature. The solvent is then removed under vacuum to obtain 2-cyclopropylcarbonyl-amido-5-chlorobenzophenone as a residue which is dissolved in 1 liter of methylene chloride, washed twice with 5% hydrochloric acid, and then twice with 10% potassium hydroxide. The methylene chloride solution is then dried over anhydrous magnesium sulfate, filtered and the solvent removed under vacuum. The residue is recrystallized from 1,500 ml of methanol, charcoal-treating the hot solution to give 356 g of 2-cyclopropylcarbonylamido-5-chlorobenzophenone, MP 105° to 105.5°C (69% yield). 

L-CCG 1, selective group II mGluR agonist, 2-(Amino-carboxy-methyl)-cyclopropane-carboxylic acid... 

Figure 5 Separation of 27 PTC AAs (column 150+ (20 guard) x 4 mm, Cl 8 Hypersil Sum, T=50°C, eluent A 0.05 mol I" NaAc, pH 7.2, B A eluent/acetonitrile/methanol = 46/44/10 (pH 7.2) flow rate 2.1 ml min peaks 1 = aspartic, 2 = glutamic acids, 3 = hy-hydroxyproline, 4 = serine, 5 = glycine, 6 = asparagine, 7 = -alanine, 8 = glutamine, 9 = homoserine, 10 = y-aminobutyric acid (GABA), 11 =histidine, 12 = threonine, 13 = alanine, 14 = 1-amino-1-cyclopropane carboxylic acid (ACPCA), 15 = arginine, 16 = proline, 17 = homoarginine, 18 = tyrosine, 19 = valine, 20 = methionine, 21 =cyst(e)ine, 22 = isoleucine, 23=n-leucine, 24 = phenyl-ylalanine, 25 = tryptophan, 26 = ornithine, 27 = lysine = system peaks. (Reproduced with permission from Vasanits A and Molnar-Perl I (2000) Journal of Chromatography A 870 271-287 Elsevier.)...

Chiral iron acyl complexes have been applied to the asymmetric synthesis of cyclopropane carboxylic acids, sulfoxides and p-amino acids. Further details and applications may be found in the reviews given in the reference... 

A route has been described for the preparation of anhydrous (J )-epi-chlorohydrin (57) from D-mannitol this epoxide could be converted (Scheme 15) into the lactone (58) by initial attack at the epoxide, and hence into (-)-(lS,2R)-l-amino-2-(hydroxymethyl)cyclopropane carboxylic acid (59) through Hoffmann reaction. 54... 

The spiropyrazohnes obtained from 51 were converted into enantiopure A -pyrazoline-3-carboxylates and 1 -(hydroxyethyl)cyclopropane-1 -carboxylates (128). Those obtained from 54 and 55 were transformed into optically active a-spirocyclopropyllactones and 3-amino-3-(hydroxyethyl)pyrrolidin-2-ones (130). The spiropyrazoline obtained from a chiral propylidene-diketopiperazine and diazomethane was converted into (+)-(lR,25)-l-amino-2-ethyl)cyclopropane-l-carboxylic acid (allocoronamic acid) (135). 

The mechanism of this unusual cis addition has not been clarified. The bromoethyl derivative 2 can be further alkylated (intramolecularly) to give the deuterated cyclopropyl derivative 3. Once again, cis addition predominates, with 46% de. Upon hydrolysis of the cyclopropyl derivative, optically active (V)-l-amino-cyclopropane-2-r/2-l-carboxylic acid (4) in 44% yield and 46% ee is obtained. 

Liirssen, K., Naumann, K. Schroder, R. (1979). 1-Amino-cyclopropane-l-carboxylic acid - an intermediate of ethylene biosynthesis in higher plants. Zeitschrift fur Pflanzenphysiologie 92, 285-94. 

The biosynthetic pathway of coronatine has been extensively studied. The coronafacic acid moiety is proposed to be constructed by bacterial modular type-I PKS via 5-oxocyclopentene carboxylic acid. A recent study clarified the detailed mechanism of the formation of highly unusual cyclopropane amino acid via D-3-chloroalloisoleucine (enzyme-bound form).307... 

In contrast to the restricted occurrence of the secondary metabolites mentioned previously, all plants contain 1-amino-cyclopropane-l-carboxylic acid. This amino acid is the precursor of ethylene. In the course of the bios)mthesis of this gaseous phytohormone, 1-aminocyclopropane-l-carboxylic acid is oxidized and decomposed to yield ethylene, HCN, CO2 and water (John, 1997). 

Most of the compounds cited in this introductory section are produced in metabolic processes where the cyclopropane-containing metabolite appears to be the stable end product or secondary product with as yet unobvious metabolic function. However, this is not the case in at least two types of systems, in which cyclopropyl species are key and necessary intermediate structures in high flux metabolic pathways. The first example is the squalene (76) and phytoene (88) biosynthesis where presqualene pyrophosphate (77) and prephytoene pyrophosphate (89) are obligate cyclopropanoid intermediates in the net head-to-head condensations of two farnesyl pyrophosphate (73) or two geranylgeranyl pyrophosphate (66) molecules respectively. The second example is in plant hormone metabolism where C(3) and C(4) of the amino acid methionine are excised as the simple hormone ethylene via intermediacy of 1-aminocyclopropane-l-carboxylic acid (9). Both examples will be discussed in detail in the Section II. 

The second chirality source used in the synthesis of aminocyclopropane carboxylic acids was D-glyceraldehyde acetonide, which after Wittig-Homer-Emmons reaction provided the alkenes 61. Treatment with diazomethane and subsequent irradiation at low temperatures alforded the cyclopropanes 62, which were converted into several other derivatives by modification of the side chain (Scheme 11). Notably, the best results were obtained by irradiating in the presence of benzophenone as triplet sensitizer [33, 34]. Following a similar synthetic procedure allocoronamic acid 65 was prepared, which is one of the amino acids that can be processed by plant tissues and promises the possibility to control the enzymatic processes underlying plant growth and fruit ripening [35]. 

Fig. Id. Ethylene Exhylcnt 1-amino-cyclopropane-1-carboxylic acid (ACC).

Fig. 8. Possible interactions of four stereo isomers of l-amino-2-ethyl-cyclopropane-l-carboxylic acid (AEC) with ACC oxidase. Functional groups of AEC which interact with enzyme are underlined, and only (lR,2S)-isomer properly interacts with enzyme. 

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