Amino instability

Dieckmann reaction, 4, 471 Indolizidine alkaloids mass spectra, 4, 444 Indolizidine immonium salts reactions, 4, 462 Indolizi dines basicity, 4, 461 circular dichroism, 4, 450 dipole moments, 4, 450 IR spectra, 4, 449 reactivity, 4, 461 reviews, 4, 444 stereochemistry, 4, 444 synthesis, 4, 471-476 Indolizine, 1-acetoxy-synthesis, 4, 466 Indolizine, 8-acetoxy-hydrolysis, 4, 452 synthesis, 4, 466 Indolizine, I-acetyl-2-methyI-iodination, 4, 457 Indolizine, 3-acyloxy-cyclazine synthesis from, 4, 460 Indolizine, alkyl-UV spectra, 4, 449 Indolizine, amino-instability, 4, 455 synthesis, 4, 121 tautomerism, 4, 200, 452 Indolizine, 1-amino-tautomerism, 4, 38 Indolizine, 3-amino-synthesis, 4, 461, 470... 

Both 2- and 3-nitrothiophenes are reduced by tin and hydrochloric acid to the corresponding aminothiophenes. In contrast to anilines, the free bases are very unstable their salts and acyl derivatives, however, are stable. 2-Aminothiophene can be diazotized and the resulting diazonium salt coupled with /3- naphthol. The chemical instability of aminothiophenes compared with aniline is illustrated by the ring opening of 2-amino-3-ethoxycar-bonylthiophenes (157) with ethanolic sodium ethoxide to give cyanothiolenones (158) <75JPR861). 

Aminofurans substituted with electron-withdrawing groups e.g. NO2) are known and 3-amino-2-methylfuran is a relatively stable amine which can be acylated and diazotized. 2-Amino-3-acetylfurans are converted into 3-cyano-2-methylpyrroles on treatment with aqueous ammonia. This transformation is a further illustration of the relative instability of the amino derivatives of five-membered ring heterocycles compared with anilines (Scheme 67) (781003821). 

A number of drawbacks in the application of the 0PA/2-ME reagent system include the instability of the fluorescent isoindole derivative (5-7) the use of the noisome reagent 2-mercaptoethanol the low and solvent-dependent fluorescence efficiencies (8,9) of the isoindole and—perhaps the most limiting—the effective restriction of the OPA assay to primary aliphatic amines and to amino acids. 

The Rieske protein in mitochondrial bci complexes is assembled when the protein is incorporated into the complex. The Rieske protein is encoded in the nucleus and synthesized in the cytosol with a mitochondrial targeting presequence, which is required to direct the apoprotein to the mitochondrial matrix. The C-terminus is then targeted back to the outside of the inner mitochondrial membrane where the Rieske cluster is assembled. In addition, the presequence is removed and the protein is processed to its mature size after the protein is inserted into the bci complex. In mammals, the presequence is cleaved in a single step by the core proteins 1 and 2, which are related to the general mitochondrial matrix processing protease (MPP) a and (3 subunits the bovine heart presequence is retained as a 8.0 kDa subunit of the complex (42, 107). In Saccharomyces cerevis-iae, processing occurs in two steps Initially, the yeast MPP removes 22 amino acid residues to convert the precursor to the intermediate form, and then the mitochondrial intermediate protease (MIP) removes 8 residues after the intermediate form is in the bci complex (47). Cleavage by MIP is independent of the assembly of the Rieske cluster Conversion of the intermediate to the mature form was observed in a yeast mutant that did not assemble any Rieske cluster (35). However, in most mutants where the assembly of the Rieske cluster is prevented, the amount of Rieske protein is drastically reduced, most likely because of instability (35, 44). 

Enantiopure a-amino aldehydes are valuable synthons in natural product synthesis [57]. However, problems are often encountered with their configurational instability [58]. Aziridine-2-carboxaldehydes are also a-amino aldehydes and accordingly have a potential synthetic value. We found that M-tritylaziridine-2-carboxaldehyde 56 is a perfectly stable compound and therefore comparable to Garner s aldehyde (ferf-butyl 2,2-dimethyl-4-(S)-formyl-oxazolidine-3-car-boxylate). Aldehyde 56 can readily be prepared from aziridine-2-carboxylic ester 12 by the sequence shown in Scheme 42 [59]. 

Fukuoka was found to be homozygous for the 1615 G to A (539 Asp to Asn) mutation. This mutation occurred at relatively conserved amino acid residues and caused an alteration in hydrophobicity. Recently, we examined the structure-function relationship of these variants using the recombinant protein (F14). Although all of the four variants were found to be heat labile, the residual GPI activity seems to reflect clinical severity, such as the degree of anemia and episodes of hemolytic crisis. GPI Matsumoto, associated with severe anemia and hemolytic crisis, was extremely unstable, and GPI Iwate, which is associated with compensated hemolytic anemia, showed moderate heat instability. Affinity for substrate, fructose-6-phosphate, was slightly decreased in GPI Narita and GPI Fukuoka, which were associated with moderate anemia and hemolytic crisis. 

Undoubtedly because of its chemical instability, examples of a secondary CF2 group bound to amino nitrogen are rare, with a chemical shift being reported only for PhCF2N(CH3)2 (-72 ppm). 

This, and the corresponding 5-chloro and 5-methoxy derivatives, tend to explode during vacuum distillation, and minimal distillation pressures and temperatures are recommended. This instability, (which was not noted for the homologues in which the hydrogen atom of the secondary amino group was replaced by alkyl) may be connected with the possibilty of isomerisation to the ac7-nitro iminoquinone internal salt species. 

E. L. Shock (1990) provides a different interpretation of these results he criticizes that the redox state of the reaction mixture was not checked in the Miller/Bada experiments. Shock also states that simple thermodynamic calculations show that the Miller/Bada theory does not stand up. To use terms like instability and decomposition is not correct when chemical compounds (here amino acids) are present in aqueous solution under extreme conditions and are aiming at a metastable equilibrium. Shock considers that oxidized and metastable carbon and nitrogen compounds are of greater importance in hydrothermal systems than are reduced compounds. In the interior of the Earth, CO2 and N2 are in stable redox equilibrium with substances such as amino acids and carboxylic acids, while reduced compounds such as CH4 and NH3 are not. The explanation lies in the oxidation state of the lithosphere. Shock considers the two mineral systems FMQ and PPM discussed above as particularly important for the system seawater/basalt rock. The FMQ system acts as a buffer in the oceanic crust. At depths of around 1.3 km, the PPM system probably becomes active, i.e., N2 and CO2 are the dominant species in stable equilibrium conditions at temperatures above 548 K. When the temperature of hydrothermal solutions falls (below about 548 K), they probably pass through a stability field in which CH4 and NII3 predominate. If kinetic factors block the achievement of equilibrium, metastable compounds such as alkanes, carboxylic acids, alkyl benzenes and amino acids are formed between 423 and 293 K. 

The authors showed that it was possible to perform this reaction in a multimode microwave oven [19] in a few minutes on a large scale in water containing a slight excess of potassium hydroxide but without cosolvent. Under the action of classical heating the major problem with these syntheses is the instability of the thiophene o-amino acids, which readily decarboxylate at room temperature to give aminothio-phenes which are themselves unstable [20 a] and have to be used as soon as they are prepared. With large quantities of reactants, moreover, the hydrolysis step is not easy to perform because of the low reactivity of thiophene carboxylates 39 and 42 [20 b]. 

As stated previously, the total normal cytoplasmic free copper concentration is less than 10 18 M or less than one copper ion per cell. In thermodynamic terms, almost all hydrated copper ions are immediately and tightly coordinated by amino acids or biopolymers—peptides, proteins, and other species with free sulfur ligands. An excess of copper ions activates metallothionein synthesis for storage or removal of the excess. Copper chaperones mediate transfer of copper ions from extracellular or storage locations to their target proteins. Instability of copper ion concentrations in vivo results in various disease states. Three of these—FALS, Menkes, and Wilson s diseases—are described below. 

Derivatization of primary amino acids with o-phthalaldehyde (OPA) is simple and the poor reproducibility due to the instability of the reaction product can be improved by automation and the use of alternative thiols, e.g. ethanthiol in place of the 2-mercaptoethanol originally used. An alternative fluorimetric method using 9-fluoroenylmethylchloroformate (FMOC-CL) requires the removal of excess unreacted reagent prior to column chromatography. This procedure is more difficult to automate fully and results are less reproducible. However, sensitivity is comparable with the OPA method with detection at the low picomole or femtomole level, and it has the added advantage that both primary and secondary amino acids can be determined. 

The unusual amino acid (S)-2-amino-(Z)-3,5-hexadienoic acid (269), which is a component of the toxic y-glutamyl dipeptide isolated from the defensive glands of the Colorado beetle [209], has been synthesized along Scheme 17, after two initial attempts had proved unsuccessful due to the instability of 269 towards various oxidation conditions [210]. Scheme 17 relies on the hydrolysis of an ortho ester to generate the required carboxylic acid. Thus, the L-serine aldehyde equivalent 270 was treated with ( )-l-trimethylsilyl-l-propene-3-boronate to give the addition product 271. Reaction of 271 with KH gave the stereochemically pure (Z)-diene 272. Mild acid treatment of 272 followed by... 

A further remarkable finding in the hydrolysis of aflatoxin B1 exo-8,9-epoxide is the relative instability of the dihydrodiol, which under basic conditions exists in equilibrium with an aflatoxin dialdehyde, more precisely a furofuran-ring-opened oxy anionic a-hydroxy dialdehyde (10.134, Fig. 10.30). The dihydrodiol is the predominant or exclusive species at pH < 7, whereas this is true for the dialdehyde at pH >9, the pK value of the equilibrium being 8.2 [204], The dialdehyde is known to form Schiff bases with primary amino groups leading to protein adducts. However, the slow rate of dialdehyde formation at physiological pH and its reduction by rat and human aldo-keto reductases cast doubts on the toxicological relevance of this pathway [206]. 

---