Solid phase synthesis of structurally diverse tetra substituted pyrimidines for potential use in combinatorial chemistry

A new pyrimidine based scaffold has been identified for generation of combinatorial libraries using solid phase technique. The utility of the scaffolds was demonstrated by synthesizing small libraries of 12 substituted pyrimidines (4a-4l).     

固相有机合成

综述了近年来固相有机合成中采用的连接分子和连接策略及固相合成在有机合成中的应用。     

All valence-electrons calculations on purines and pyrimidines

An iterative extended Hückel calculation (IEHC) has been performed for the purine and pyrimidine bases of the nucleic acids. The results presented concern the electron distribution and the dipole moments, the atomic orbital populations and the hybridization ratios, the energies of the molecular orbitals and the ionization potentials. In particular, the relative orders of the dipole moments and of the -ionization potentials are correctly reproduced but their absolute values are too great.

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Zusammenfassung Die Purin- und Pyrimidinbasen der NukleinsÄuren wurden mit einer IEHC-NÄherung berechnet. Es werden die Elektronenverteilungen, die Dipolmomente, die AO-Population, die Hybridisierungskonstanten, die MO-Energien und die Ionisationspotentiale angegeben. Die Reihenfolge der Dipolmomente und -Ionisationspotentiale wird richtig erhalten.

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Résumé La méthode de Hückel étendue itérative a été utilisée pour l'étude de la structure électronique des bases puriques et pyrimidiques des acides nucléiques. Les résultats présentés concernent la distribution des charges électriques et les valeurs des moments dipolaires, les populations des orbitales atomiques et les constantes d'hybridation, les énergies des orbitales moléculaires et les valeurs des potentiels d'ionisation. En particulier, les valeurs des moments dipolaires et des potentiels d'ionisation tout en étant dans le bon ordre relatif sont trop élevées en valeur absolue.

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This work was supported by grant No. GM-12229 of the U.S. Public Health Service (National Institute of General Medical Sciences).     

Solid phase synthesis of a molecular library of pyrimidines, pyrazoles, and isoxazoles with biological potential

A small molecular library of 40 pyrimidine, pyrazole, and isoxazole derivatives, bearing structural features for a promising binding of therapeutically interesting enzymes, was designed and prepared. An efficient and straightforward solid phase synthesis was envisaged and carried out on a Rink amide resin. The assistance of microwave heating in any step reduced the reaction time, increased the reaction yields, and allowed an easy work-up and purification of the targeted compounds.     

Laser Raman spectroscopy of irradiated purines and pyrimidines

The laser Raman spectra of irradiated crystalline uracil and guanine show changes compared to that of the unirradiated compounds which are believed to be due to the production of ionic species. The Raman spectrum crystalline guanine is presented for the first time.     

Solid phase synthesis of praziquantel

The first solid phase synthesis of the important anthelmintic praziquantel is described. The synthesis is rapid and efficient. The method may be extended to the synthesis of libraries of urgently needed replacements for this drug.     

Solid phase synthesis of cyclopropenes

Cyclopropene derivatives of high purity were prepared by reaction of acetylenes with a rhodium carbenoid bound to a polystyrene resin. This solid phase method avoids the formation of undesired byproducts obtained in the corresponding solution reaction and an eventual extension to combinatorial synthesis of cyclopropene derivatives could be achieved.     

All valence-electrons calculations of the biological purines and pyrimidines

A calculation of the electronic structure of the bases of DNA has been performed by an SCF procedure including simultaneously all the valence electrons. The results are analyzed and compared to those of previous calculations made in the electron approximation.

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Zusammenfassung Die Elektronenstrukturen der DNA-Basen werden mit einer SCF-Methode unter Einschluß aller Valenzelektronen untersucht. Die Ergebnisse werden mit denen reiner -Rechnungen verglichen.

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Résumé Un calcul de la structure électronique des bases de l'acide déoxyribonucléique a été effectué par un procédé self-consistent traitant tous les électrons de valence simultanément. Les résultats sont analysés et comparés à ceux de calculs antérieurs faits dans l'approximation de la séparation -.

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This work was supported by grant no. 67-00-532 of the Délégation Générale à la Recherche Scientifique et Technique (Comité de Biologie Moléculaire).     

The synthesis of carboxymethyl derivatives of purines and pyrimidines and their condensation with naturally occurring macromolecules

1-Carboxymethylthymine, 1-carboxymethylcytosine and 9-carboxymethyladenine were obtained by the direct carboxymethylation of the appropriate bases. In addition a small amount of 3-carboxymethyladenine was obtained. 9-Carboxymethylhypoxanthine was obtained by deamination of 9-carboxymethyladenine. 1-Carboxymethyluracil, 1-carboxymethylthymine and 9-carboxymethyl-hypoxanthine were each condensed with protamine and with dextran to give water-soluble, base-substituted polymers. The 1-carboxymethylthymine-dextran showed a slow decrease in optical density at 268 nm in 2 × SSC at 20°, of 30%. This did not occur in 7M urea. 1-Carboxymethylthymine-dextran gave an additional hypochromic effect with polyadenylic acid in 2 × SSC at 4° or 14° of 13% and 9% respectively. The ratio of thymine: adenine residues at the point of maximum hypochromicity was 3:1. The other dextran derivatives did not show similar hypochromic effects. The 1-carboxy-methylthymine-protamine gave a precipitate with polyadenylic acid probably due to electrostatic interaction.     

PPP calculations of the absorption spectra of purines and pyrimidines

A mechanism of the synthesis of cyclooctatetraene is discussed in which a temporary transfer of the multiplicity from the Ni²⁺ ion to the four acetylene molecules takes place.     

固相同步多重肽合成

本文综述了近十年来在固相肽合成基础上发展的各种同步多重合成新技术。它们的应用可进一步提高肽合成的效率、降低成本,并将促进许多肽的结构-活性关系研究。因此,将对激素-受体间作用的机理研究、对分子免疫学的发展及研究新的肽类诊断试剂或疫苗均可创造较好的条件。     

Facile synthesis of fused purines from 8-aminotheophylline

Fused purines 3a-f were prepared by one-step from 8-aminotheophylline ( 1 ) and α,ω-dibromoalkanes in N, N-dimethylformamide in the presence of sodium hydride. Reaction of 3c-e with chloroacetyl chloride followed by treatment with dimethylamine gave 6a-c . A one-step reaction of 1 with ethyl bromopropionate gave 1,3-dimethyl-1,2,3,4,6,7,8,9-octahydropyrimido[2,1-f]purine-2,4,8-trione ( 7b ). Facile syntheses of 7a, c, d from 1 were also carried out.     

SCF Deformation densities and electrostatic potentials of purines and pyrimidines

4-31G wave functions have been computed for five purines and pyrimidines. The calculated deformation densities have been partitioned into atomic fragments, which were integrated to yield atomic multipole moments. The transferability of atomic fragments between related molecules was verified by constructing model maps for uracil and guanine from appropriate fragments of cytosine and adenine. Model electrostatic potentials calculated from the moments of model atoms are similar to the corresponding 4-31G potentials. Comparison of 4-31G and 4-31G** deformation densities of cytosine provides simple rules for estimating the effects of polarization functions on the atomic multipole moments of most atom types occurring in the purines and pyrimidines. These rules were applied to the other molecules and yielded reasonable approximations for their molecular dipole moments. Substituting CH₃ for H has little effect on the deformation density beyond the substitution center.     

芳亚甲基丙二腈、芳亚甲基氰乙酰胺的固相合成

芳醛和丙二腈、氰乙酰胺在NH4Ac催化下经固相反应高产率的得到芳亚甲基丙 二腈和芳亚甲基氰乙酰胺。     

固相有机合成小分子化合物库

从杂环化合物库和非杂环化合物库两方面介绍了组合化学中采用固相合成技术所构建的小分子化合物库。