Simple Amine Derivatives

A major effort at utilizing the platinum-containing polymer itself as a drug is the mainchain incorporation of platinum based on the de novo synthesis of the polymer structure from specified monomers, as no presynthesis of carrier polymer is required. The preparative approach is exemplified by the polymerization of tetra-chloroplatinate(II) dianion with diamines and other nitrogen-containing compounds. 

The initial polymers containing Pt-N in the backbone were reported in 1981. The reaction was based on the synthesis of cw-DDP itself, except the nitrogen-containing reactants were diamines. Much of this work was reviewed in 1985.  

Synthesis was straightforward, accomplished by mixing together aqueous solutions containing the platinum salt and the diamine. Reaction was rapid the polymer began to precipitate from the reaction mixture in minutes. 

The products were polymeric with molecular weights in the range of 10 daltons. The products were soluble at low concentrations in DMSO. The products showed 100% inhibition of HeLa and L929 cell lines at a concentration level of 50 pg/mL. 

The viral replication of poliovirus type 1 in HeLa cells was also studied, with the product from tetrachloroplatinate(II) and 1,6-hexanediamine (14) able to effectively inhibit viral growth at a concentration level of 10 pg/mL. (The viral activity is discussed further in Section VIII.F.) The compounds were relatively nontoxic, with mice able to tolerate 400 pg/mouse (highest level tested) without noticeable ill effects.  

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Tryptophan is an essential amino acid for most organisms. In plants and bacteria, this compound is derived from chorismic acid. Many groups of secondary compounds are formed from tryptophan among these are several simple amine derivatives and a number of alkaloids. 

Simple amine derivatives apparently occur in most, if not all, plants, and the alkaloids derived from them are widespread. 

Protoalkaloids These compounds are simple amines, derived from amino acids, in which the basic nitrogen atom is not incorporated into a ring system they are often referred to as biological amines. An example of a protoalkaloid is mescaline. 

Two substituents on two N atoms increase the number of diaziridine structures as compared with oxaziridines, while some limitations as to the nature of substituents on N and C decrease it. Favored starting materials are formaldehyde, aliphatic aldehydes and ketones, together with ammonia and simple aliphatic amines. Aromatic amines do not react. Suitable aminating agents are chloramine, N-chloroalkylamines, hydroxylamine-O-sulfonic acid and their simple alkyl derivatives, but also oxaziridines unsubstituted at nitrogen. Combination of a carbonyl compound, an amine and an aminating agent leads to the standard procedures of diaziridine synthesis. 

The kinetics of the hydrolysis of some imines derived from benzophenone anc primary amines revealed the normal dependence of mechanism on pH with ratedetermining nucleophilic attack at high pH and rate-determining decomposition of the tetrahedral intermediate at low pH. The simple primary amines show a linear correlation between the rate of nucleophilic addition and the basicity of the amine Several diamines which were included in the study, in particular A, B, and C, al showed a positive (more reactive) deviation from the correlation line for the simple amines. Why might these amines be more reactive than predicted on the basis of thei ... 

The Bts derivative is formed from the sulfonyl chloride, either using apro-tic conditions for simple amines or by the Schotten-Baumann protocol for amino acids (87-97% yield). The primary drawback of this reagent is that its stability depends on its quality. It can on occasion rapidly and exothermically lose SO2 to give 2-chlorobenzothiazole. ... 

For the results reported in both Table 7.2-3 and Table 7.2-4, the only reported detail concerning the ionic liquid was that it was [EMIM][C1-A1C13]. No details of the aluminium(III) chloride content were forthcoming. As with most of the work presented in this chapter, data are taken from the patent literature and not from peer reviewed journals, and so many experimental details are not available. This lack of clear reporting complicates issues for the synthetic polymer chemist. Simpler and cheaper chloroaluminate(III) ionic liquids prepared by using cations derived from the reaction between a simple amine and hydrochloric acid (e.g., Me3N-E3Cl and... 

Simple Amines, Alcohols and Amino Acid Derived Amino Alcohols as Chiral Catalysts... 

To obtain information about the structural requirements of a ligand capable of catalyzing the addition of dialkylzincs to aldehydes, various simple amines, alcohols and amino acid derived amino alcohols were tested as chiral catalysts (Table 27). 

Hydro-de-diazoniation seems to be an unnecessary reaction from the synthetic standpoint, as arenediazonium salts are obtained from the respective amines, reagents that are normally synthesized from the hydrocarbon. Some aromatic compounds, however, cannot be synthesized by straightforward electrophilic aromatic substitution examples of these are the 1,3,5-trichloro- and -tribromobenzenes (see below). These simple benzene derivatives are synthesized from aniline via halogenation, diazotization and hydro-de-diazoniation. Furthermore hydro-de-diazoniation is useful for the introduction of a hydrogen isotope in specific positions. 

It was only around 1850 that the first amines were discovered by Wurtz [2], who considered them as alkylated (or arylated) derivatives of NH3. Nowadays, it is well known that the amine function is widespread among biologically important compounds, but mostly it is present in polyfunctional molecules such as amino acids, alkaloids, etc. Simple amines are very rare in nature, with the exception of tri-ethylamine and the trimethylammonium ion which come from the putrefaction of proteins. 

Let us now examine a simple numerical model for the mixing of substituent orbitals into the spectroscopic orbitals of the carbonyl chromophore. For this purpose we consider the triplet 3n— Tt excited state of the model amine derivative of methylethylketone shown in Fig. 3.75. 

A comparison of the initial rates obtained with various cobalt complexes (Table I) reveals that the chelate complexes of Co(II) are more efficient than the simple salts, the catalytic activity of Co(III) is lower than that of Co(II) and the reaction becomes slower by increasing the number of N atoms in the coordination spheres in both oxidation states. In general, the addition of amine derivatives increased the activity of the catalysts. 

Recently, Raju et al.6 reported an attractive method for the preparation of unsymmetrical ureas on solid-phase resins, employing nitrophenylcarbamates as the key intermediates. They used this method to synthesize ureas derived from simple amines. Here, we report that unsymmetrical ureas can be formed in high yield and purity using MicroTubes as the solid supports. 

Silicon derivatives of these simple amines have also been studied using /-irradiation in CFCI3 solution at 77 K. The radical cations 7 and 8 are formed in each of the cases. The EPR study showed that the singly filled MO of the radical cation was delocalized and extended into the silyl groups. The hydrazine derivative 9 also affords a radical cation... 

Like its monomeric counterpart, the polymeric reagent is inert to simple amines, amides, alcohols and phenols, but easily oxidizes thiols to disulphides, phosphines to phosphine oxides, hydroquinone and catechol to quinones, and thioketones, thioesters and trithiocar-bonates to the corresponding 0x0 derivatives, in dichloromethane, chloroform or acetic... 

Imines and (Af,(9)-acetals from fluoral are useful precursors of trifluoromethyl nitrogen-containing molecules amines, amino alcohols, amino acids, peptidomimetic units, heterocycles, and so on (Figure 2.50). These simple Af-derivatives of fluoral are easily prepared from the hydrate or the hemiacetal. Imines of fluoral react in [2 + 1 ]... 

As might be expected, the stability and reactivity of diazonium salts are affected by substituents as well as by the anion. The rate of coupling and the location of the azo bond are influenced by substituents on the coupling reagent. Some primary and secondary aromatic amines derived from benzene initially form A-azo compounds, which rearrange to p-aminoazo compounds in acidic media [8b, c]. Tertiary amines, on the other hand, behave normally. Preparation 2-3, while of a rather complex molecule, illustrates the simple techniques commonly used in coupling in an aqueous system. Note the presumed preferential tendency of coupling to take place predominantly in the para position. 

Many important neurotransmitters are primary or secondary amines, derived from amino acids in simple pathways. In addition, some polyamines that form complexes with DNA are derived from the amino acid ornithine, a component of the urea cycle. A common denominator of many of these pathways is amino acid decarboxylation, another PLP-requiring reaction (see Fig. 18-6). 

One of the earliest comparisons of thiophene to benzene in a biological system compared the vasoconstrictor activity of phenylethylamine (362 Ar = Ph) with that of 2-thienyIethyl-amine (362 Ar = 2-thienyl). It was shown to have vasopressor activity in the cat, but was only about one-tenth as potent. Phenylalanine is an essential amino acid for the growth of yeast, bacteria and mammals. It was found that /3-2-thienylalanine (363 Ar = 2-thienyl) was an antimetabolite of this essential amino acid, and numerous studies on the active L-form and simple peptides derived from it have been made. 

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