“Tied-back” carbocyclic intermediates in the preparation of very sterically strained olefins: Derivatives of tetra-tert-butylethylene

The preparations of the extremely sterically hindered olefins (12) and-(13) are described, and attempts to convert these compounds to other derivatives of tetra-$\text{tert}$-butylethylene (1) are outlined.     

A structure-based 3D-QSAR study of anthrapyrazole analogues of the anticancer agents losoxantrone and piroxantrone

A series of 13 anthrapyrazole compounds that are analogues of piroxantrone and losoxantrone were synthesized, and their cell growth inhibitory effects, DNA binding, topoisomerase IIalpha mediated (EC 5.99.1.3) cleavage of DNA, and inhibition of DNA topoisomerase IIalpha decatenation catalytic activities were determined. Cell growth inhibitory activity was well-correlated with DNA binding, suggesting that these compounds may act by targeting DNA. However, cell growth inhibition was not well-correlated with the inhibition of topoisomerase IIalpha catalytic activity, suggesting that these anthrapyrazoles did not act solely by inhibiting the catalytic activity of topoisomerase II. Most of the analogues were able to induce DNA cleavage, and thus, it was concluded that they acted, at least in part, as topoisomerase II poisons. Structure-based three-dimensional quantitative structure-activity analyses (3D-QSAR) were carried out on the aligned structures of the anthrapyrazoles docked into DNA using comparative molecular field analysis (CoMFA) and comparative molecular similarity index (CoMSIA) analyses in order to determine the structural features responsible for their activity. Both CoMFA and CoMSIA yielded statistically significant models upon partial least-squares analyses. The 3D-QSAR analyses showed that hydrogen-bond donor interactions and electrostatic interactions with the protonated amino side chains of the anthrapyrazoles led to high cell growth inhibitory activity.     

A convenient reductive deamination (hydrodeamination) of aromatic amines.

Reductive deamination (hydrodeamination) of aromatic amines can be conveniently carried out by amination of the corresponding arylamine methanesulfonamides using chloroamine under alkaline conditions. The intermediate aryl methanesulfonylhydrazines directly eliminate methanesulfinic acid, affording diazenes which extrude nitrogen affording the desired deaminated products. Both sulfonamide formation and reduction reactions occur in high yield and are compatible with a variety of functional groups.     

Selones as intermediates in the preparation of extremely sterically hindered molecules

The preparation and reactions of selones, selenium analogues of ketones, are described with particular emphasis on their utility in the preparation of extremely sterically hindered molecules. Mechanistic questions related to these reactions are discussed and evidence for “active selenium” is presented. Selenophilic additions of organometallic compounds to selones are also reported.     

Photochemical transformations of 4,5-diaryl-4-oxazolin-2-one protecting groups

The photochemical cleavage of 4,5-diaryl-4-oxazolin-2-one protecting groups is discussed as an alternative to reduction or chemical oxidation of the heterocyclic system. Ultraviolet irradiation in air of oxazolinone ( 1 ) in methanol leads to photooxygenation of the protecting group, affording the corresponding benzamide and benzoate ester. Reduction of the intermediate photoproduct leads to complete removal of the protecting group. A mechanism for this photolysis is proposed and evidence in support of this mechanism is reported.     

The chiroptical properties of selenofenchone,a selenoketone with an asymmetrically perturbed CSe chromophore

CD, ORD, and UV spectra were obtained for the first time on a selenoketone; the chiroptical properties of the selenoketone and of its analogous thione and ketone were parallel.     

Synthesis of the cyclobutanone core of solanoeclepin A intramolecular allene butenolide photocycloaddition

The compact tricyclic substructure of solanoeclepin A containing the cyclobutanone ring was prepared by using as the key step a highly regioselective intramolecular [2 + 2]-photocycloaddition reaction between one of the [small pi]-bonds of an allene and the CC double bond of a butenolide.     

Evaluation of relative DNA binding affinities of anthrapyrazoles by electrospray ionization mass spectrometry

Binding interactions of a new series of anthrapyrazoles (APs) with DNA were evaluated by electrospray ionization mass spectrometry (ESI-MS). Relative binding affinities were estimated from the ESI-MS data based on the fraction of bound DNA for DNA/anthrapyrazole mixtures, and they show a correlation to the shift in melting point of the DNA measured from a previous study. Minimal sequence specificity was observed for the series of anthrapyrazoles. Upon collisionally activated dissociation of the duplex/anthrapyrazole complexes, typically ejection of the ligand was the dominant pathway for most of the complexes. However, for complexes containing AP2 or mitoxantrone, strand separation with the ligand remaining on one of the single strands was observed, indicative of a different binding mode or stronger binding.