Tamer T. El-Idreesy

Photooxygenation of allylic alcohols: kinetic comparison of unfunctionalized alkenes with prenol-type allylic alcohols, ethers and acetates

The kinetics of the chemical and physical quenching of the first excited singlet state of oxygen [1O2 (1delta(g))] by unfunctionalized alkenes 1-4, allylic alcohols 5-7 and 9, allylic acetates 8 and 11, and the allylic ether 10 display small solvent-polarity effects on the reactivity. The regioselectivity of the singlet oxygen ene reaction is solvent independent for the unfunctionalized alkenes as well as the prenol-type substrates, the latter showing substantial solvent effects on the diastereoselectivity. Pronounced physical quenching is detected only for the allylic alcohols 5 and 6. These results are interpreted in terms of the interactions between singlet oxygen and the allylic hydroxy groups, conformationally promoted by allylic strain which lead either to chemical activation or to physical quenching. The results for substrate 9 in deuterated v.s non-deuterated methanol are in accord with hydrogen bonding between the allylic alcohol and 1O2, which directs the diastereoselectivity of the ene reaction with chiral allylic alcohols.

Photooxygenation in polymer matrices: En route to highly active antimalarial peroxides

Photooxygenation involving the first excited singlet state of molecular oxygen is a versatile method for the generation of a multitude of oxy-functionalized target molecules often with high regio- and stereoselectivities. The efficiency of singlet-oxygen reactions is largely dependent on the nonradiative deactivation paths, mainly induced by the solvent and the substrate intrinsically. The intrinsic (physical) quenching properties as well as the selectivity-determining factors of the (chemical) quenching can be modified by adjusting the microenvironment of the reactive substrate. Tetraarylporphyrins or protoporphyrin IX were embedded in polystyrene (PS) beads and in polymer films or covalently linked into PS during emulsion polymerization. These polymer matrices are suitable for a broad variety of (solvent-free) photooxygenation reactions. One specific example discussed in detail is the ene reaction of singlet oxygen with chiral allylic alcohols yielding unsaturated β-hydroperoxy alcohols in (threo) diastereoselectivities, which depended on the polarity and hydrogen-bonding capacity of the polymer matrix. These products were applied for the synthesis of mono- and spirobicyclic 1,2,4-trioxanes, molecules that showed moderate to high antimalarial properties. Subsequent structure optimization resulted in in vitro activities that surpassed that of the naturally occurring sesquiterpene-peroxide artemisinin.

Computational and experimental evidence for the first direct spectroscopic detection of the pyrylogen neutral redox partner.

The first synthesis of the two-electron reduction product of a pyrylogen is reported. The magnitude of the experimentally determined disproportionation constant for a pyrylogen radical cation was used to advantage in order to provide compelling evidence for formation of this reduction product. Computational studies were used to provide verification of these results and to provide additional insight into the pyrylogen redox system.

Hydrolytic Stability of N-Methyl-2,6-dimesityl-4,4′-Pyrylogen Bis-tetrafluoroborate

The synthesis and characterization of a new mesityl ring-substituted pyrylogen with a substantially decreased rate of reaction with water is reported. Computational and experimental data are presented that suggest that addition of water to the pyrylium ring of this highly sterically shielded pyrylogen is reversible. On the other hand, experimental data suggest that the overall hydrolysis of this new sterically shielded pyrylogen, but not the parent pyrylogen, is irreversible. Two potential explanations for this behavior are presented and discussed. These results provide important new information that can be used to design and synthesize new electron transfer sensitizers that can be used even in highly aqueous environments.

Synthesis, biological evaluation, and molecular docking studies of new pyrazol-3-one derivatives with aromatase inhibition activities.

A new series derived from 4‐(2‐chloroacetyl)‐1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3H‐pyrazol‐3‐one was synthesized, characterized and its pharmacological activity toward aromatase enzyme inhibition was screened and compared to the reference native ligand letrozole. The most active compound of the series was 16, showing IC50 value of 0.0023 ± 0.0002 μm compared to letrozole with IC50 of 0.0028 ± 0.0006 μm. In addition, compounds 26 and 36 exhibit good inhibition activities close to letrozole with IC50 values 0.0033 ± 0.0001 and 0.0032 ± 0.0003 μm, respectively. Moreover, molecular docking studies were conducted to support the findings.

1,2,5,10,11,14-Hexaoxadispiro[5.2.5.2]hexadecanes: Novel Spirofused Bis-Trioxane Peroxides

A set of new bis-spirofused 1,2,4-trioxanes 4a-d was obtained from the reaction of cyclohexane-1,4-dione with allylic hydroperoxides 2a-d, bearing an additional hydroxy group in the homoallylic position, by diastereoselective photooxygenation of allylic alcohols 1a-d and subsequent BF3-catalyzed peroxyacetalization with the diketone. From the reaction of a monoprotected cyclohexane-1,4-dione 5 with the allylic hydroperoxide 6 derived from the singlet oxygenation of methyl hydroxytiglate, one monospiro compound was obtained, the 1,2,4-trioxane ketone 7, as well as a mixture of the diastereoisomeric syn- and anti bis-1,2,4-trioxanes 8. The structures of bis-1,2,4-trioxanes were examined theoretically by DFT methods and compared with X-ray structural data in order to evaluate the preferential trioxane ring conformational orientation.