In a search of small molecules active against apoptosis-resistant cancer cells, a skeletal rearrangement of alkaloid haemanthamine was utilized to generate a series of compounds possessing the alkaloid montanine ring system. The synthesized compounds were found to inhibit proliferation of cancer cells resistant to apoptosis at micromolar concentrations. Selected compounds were also active against patient-derived glioblastoma cells expressing stem-cell markers. This is the first report describing the preparation of synthetic analogues of the montanine-type alkaloids with antiproliferative activity. The compounds prepared in the current investigation appear to be a useful starting point for the development of agents to fight cancers with apoptosis resistance, and thus, associated with poor prognoses.

Two examples of core-modified 36π doubly fused octaphyrins that undergo a conformational change from a twisted figure-eight to an open-extended structure induced by protonation are reported. Syntheses of the two octaphyrins (in which Ar=mesityl or tolyl) were achieved by a simple acid-catalyzed condensation of dipyrrane unit containing an electron-rich, rigid dithienothiophene (DTT) core with pentafluorobenzaldehyde followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The single-crystal X-ray structure of the octaphyrin (in which Ar=mesityl) shows a figure-eight twisted conformation of the expanded porphyrin skeleton with two DTT moieties oriented in a staggered conformation with a π-cloud distance of 3.7 Å. Spectroscopic and quantum mechanical calculations reveal that both octaphyrins conform to a [4n]π nonaromatic electronic structure. Protonation of the pyrrole nitrogen atoms of the octaphyrins results in dramatic structural change, which led to 1) a large redshift and sharpening of absorption bands in electronic absorption spectrum, 2) a large change in chemical shift of pyrrole β-CH and -NH protons in the (1)H NMR spectrum, 3) a small increase in singlet lifetimes, and 4) a moderate increase in two-photon absorption cross-section values. Furthermore, nucleus-independent chemical shift (NICS) values calculated at various geometrical positions show positive values and anisotropy-induced current density (AICD) plots indicate paratropic ring-currents for the diprotonated form of the octaphyrin (in which Ar=tolyl); the single-crystal X-ray structure of the diprotonated form of the octaphyrin shows an extended structure in which one of the pyrrole ring of each dipyrrin subunit undergoes a 180° ring-flip. Four trifluoroacetic acid (TFA) molecules are bound above and below the molecular plane defined by meso-carbon atoms and are held by N-H···O, N-H···F, and C-H···F intermolecular hydrogen-bonding interactions. The extended-open structure upon protonation allows π-delocalization and the electronic structure conforms to a [4n]π Hückel antiaromatic in the diprotonated state.

Take the shortcut: The synthesis of core-modified meso aryl hexaphyrins with an internal thiophene bridge is reported. Introduction of the thiophene bridge alters the electronic structure as well as the π-electron circuit, resulting in increases in singlet lifetime (τ(s)) and the two-photon absorption (TPA) cross-section. Furthermore, for the sulfur derivative, the internal bridging thiophene participates in a π-electron conjugation pathway.

No abstract

Two new, fused core-modified expanded porphyrins, sapphyrins 3 and 4, were synthesized by a simple acid-catalyzed condensation of electron-rich and rigid precursor, dithienothiophene (DTT) diol, and core-modified tripyrrane. These sapphyrins exhibit structural diversity depending upon the heteroatom present in the macrocyclic framework, where the thiophene ring is inverted in 3, while the selenophene ring in 4 exists in normal and inverted form in the free base and addition of two protons shifts the equilibrium to inverted form.