Band 16, Heft 4-6

No abstract available

The reaction of 3-alkyl-2,4-pyrrolidinediones with 1,1-diarylethenes in the presence of a catalytic amount of manganese(III) acetate resulted in the aerobic endoperoxidation that produced very stable crystalline 8-aza-1-hydroxy-2,3-dioxabicyclo[4.3.0] nonan-7-ones in high yields.

Fluorescence lifetime and photoacoustic imaging (PAI) provide attractive strategies for in vivo molecular imaging in the near infrared (NIR) region. Pyrrolopyrrole cyanine (PPCy) dyes are promising molecules for these applications. In this study, we synthesized a chloro-functionalized non-fluorescent dye with high absorption coefficient suitable for PAI. Upon complexation with boron, the dye becomes highly fluorescent with lifetime of 3.6 ns, which is longer than most cyanine dyes commonly used for NIR optical imaging. The potential to use the non-fluorescent or fluorescent analogs of PPCy for fluorescence or photoacoustic imaging provides a versatile approach to image molecular processes and physiological events by these methods.

The kinetic isotope effects for the oxidation of a series of deuterated isopropanols and α-trideuteromethyl benzyl alcohol by dimethyldioxirane ( 1 ) to the corresponding ketones were determined in dried acetone at 23°C. A primary kinetic isotope effect (PKIE) of 5.2 for the oxidation of isopropyl-2-d alcohol by 1 was obtained. The SKIEs for oxidation of α-trideuteromethyl benzyl alcohol and isopropyl-1,1,1,3,3,3-d 6 alcohol were found to be 1.07 and 0.98, respectively. Oxidation of isopropanol-d by 1 yielded a k OH /k OD value of 1.12, which is similar to that previously reported for α-methylbenzyl alcohol-d. Both normal and inverse secondary kinetic isotope effect (SKIEs) are observed. Mechanistically, the results indicate that the process is more complex than the previously proposed models.

Hairpin polyamide analogs of distamycin A ( 1 ) were designed and synthesized to evaluate their ability to bind 5′-ATAGA-3′ and 5′-AGATA-3′ sequences which are important elements for controlling the function of the Brn-3b and GATA-3 transcriptional factors, respectively. The hairpin polyamides are composed of pyrrole and imidazole units linked together via a γ-aminobutyrate (GABA) unit. Hairpins 2b (Py-Py-Im-γ-Py-Py-Py) and 2c (Im-Py-Py-γ-Py-Py-Py) were synthesized to target the respective Brn-3b and GATA-3 cognate sequences. Preliminary biophysical studies including thermal denaturation and circular dichroism were performed and the results ascertained the binding of hairpins 2a and 2b to their respective cognate DNA sequences.

The biophysical and biological evaluations of DNA minor groove binding AT sequence selective benzimidazole analogs of Hoechst 33258 which contain a p -anisyl, a p -[bis(2-chloroethyl)amino]phenyl or a p -anisyl and an amidine moiety are discussed. The preference for all three compounds for the 5′-AAATTT-3′ sequence was ascertained by thermal denaturation and circular dichroism studies. The mustard-containing compound 4 was found to be more cytotoxic against murine cancer cells grown in culture than the non-mustard containing compound. DNA alkylation was not necessary for anti- Leishmanial activity.

Site-specific modifications of peptides provide a powerful tool for design of chemical probes and enzyme inhibitors. A convenient synthesis method was developed and used to produce H4K16-pantetheine bisubstrate analogs which could be employed as inhibitors of histone acetyltransferases in vivo and in vitro .

Amodiaquine is one of the most active antimalarial 4-aminoquinoline. Previously we have described new analogs of amodiaquine and amopyroquine, in which the hydroxyl group was replaced by various amino groups and identified highly potent compounds. Here we describe a more efficient synthesis of this family of compounds allowing the rapid and convergent access of new analogs bearing a piperazine or a morpholine ring at the 4′-position and diverse heterocyclic amino side chains.

A rapid and efficient synthesis of fused polyphenolic/polymethoxy benzofurans and benzothiophenes that have potential as antitumor agents and components of anti-HIV combination therapy has been achieved.

6 H -Isoindolo[2,1-α]indol-6-one, a core structure for a number of biologically active compounds, was synthesized in four steps. The approach is metal-free and uses a Beckmann rearrangement followed by an intramolecular cyclization.

The synthesis of a series of substituted benzofurans is reported. Selected compounds have been shown to bind strongly and with high selectivity to the serotonin receptor 5-HT 2A in the presence of the receptor 5-HT 7 in vitro .

The crystal structure determinations and theoretical calculations at DFT/B3LYP/6-311++G(d,p) level of 5,5′-bi-1,2,4-triazine thiacrown ethers containing 16-, 19- and 22-membered macrocyclic ring were used to analyze their conformational preferences in the crysalline state and gaseous phase.

Imines of 7-dialkylamino-3-formyl-4-hydroxycoumarins have been found to exist in Z -ketoenamine form in crystal state and undergo Z/E -isomerization around C=C bond in organic solvents at room temperature. Activation energies of isomerization have been measured experimentally and calculated by the DFT B3LYP method. Transition of ketoenamine form of p -nitrophenylimines into (hydroxy)imine form at low concentration (10 -5   m ) in polar solvents is accompanied by strong increase in fluorescence.

The experimental chemical shifts and coupling constants of five borates of general formula BH n Pz 4–n [from the borohydride to tetrakis(pyrazol-1-yl)borate] anions were compared with calculations carried out at the B3LYP/6-311++G(d,p) level (GIAO for absolute shieldings), in general with satisfying results. The most stable conformations of pyrazolylborate anions are similar to those of neutral pyrazolylmethanes.

Novel thymidine derivatives carrying dimeric, tetrameric and hexameric aromatic oligoamide moieties with the backbone rigidified by the intramolecular three-center hydrogen bonds have been synthesized as potential hosts for specific molecular recognition.

Reaction of 2-thiazolidinethione with halohydrocarbon in ethanol gave a series of N -alkylated 2-thiazolidinethione and S -alkylated thiazoline derivatives in excellent yields. The reaction was carried out under mild conditions using NaOH as a base and it did not require protection from air.