The condensation of oxazoles with dienophiles is of the diene synthesis type, the final reaction products being substituted pyridine bases. The review deals with the literature data concerning the preparative applications of the condensation and the elucidation of the theoretical features of this process. In conclusion of the review, the application of heterodiene synthesis with participation of oxazoles in the preparation of vitamin B 6 and its analogues is discussed. The bibliography comprises 38 references.
CONTENTS
Aza- and deazaanalogues of adenosine, including their 1-protonated forms (except for that of 1-deazaadenosine), were studied by computer computation to find a relationship between their molecular structures and substrate properties for the mammalian adenosine deaminase. The atomic charge distribution and maps of the electrostatic potential around their van der Waals molecular surface were calculated for these compounds using the ab initio STO-3G method. The conformational studies were carried out by the MM+ method of molecular mechanics. The mechanism that determines the substrate selectivity of mammalian adenosine deaminase is discussed. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 4; see also http://www.maik.ru.
A dinucleoside bearing an amide internucleotide C3'-CH2-C(O)-NH-C5' bond was synthesized by the interaction of 3'-deoxy-3'-carboxylmethylribothymidine-2',3'-lactone obtained by hydrolysis of 2'-O-acetyl-5'-O-benzoyl-3'-deoxy-3'-ethoxycarboxylmethylribothymidine with 5'-deoxy-5'-amino-3'-O-(tert-butyldimethylsilyl)thymidine. After standard manipulations with protective groups, the dinucleoside was converted into 3'-O-(2-cyanoethyl-N,N'-diisopropylphosphoroamidite), which was used for the synthesis of modified oligonucleotides on an automatic synthesizer. Duplex melting curves formed by modified and complementary natural oligonucleotides were measured and the melting temperatures and thermodynamic parameters of duplex formation were calculated. The introduction of one modified bond into oligonucleotides caused only an insignificant decrease in the duplex melting temperatures compared with the nonmodified ones.
The conformational models of the active site of adenosine deaminase (ADA) and its complexes in the basic state with adenosine and 13 isosteric analogues of the aza, deaza, and azadeaza series were constructed. The optimization of the conformational energy of the active site and the nucleoside bound with it in the complex was achieved in the force field of the whole enzyme (the 1ADD structure was used) within the molecular mechanics model using the AMBER 99 potentials. The stable conformational states of each of the complexes, as well as the optimal conformation of the ADA in the absence of ligand, were determined. It was proved that the conformational state that is close to the structure of the ADA complex with 1-deazaadenosine (1ADD) known from the X-ray study corresponds to one of the local minima of the potential surface. Another, a significantly deeper minimum was determined; it differs from the first minimum by the mutual orientation of side chains of amino acid residues. A similar conformational state is optimal for the ADA active site in the absence of the bound ligand. A qualitative correlation exists between the values of potential energies of the complexes in this conformation and the enzymatic activity of ADA toward the corresponding nucleosides. The dynamics of conformational conversions of the active site after the binding of substrate or its analogues, as well as the possibility of the estimation of the inhibitory properties of nucleosides on the basis of calculations, are discussed.
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