Synthesis of Phenanthro[9,10-c]thiophenes by 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-Promoted Cyclo-Oxidation.

A new method to prepare phenanthro[9,10-c]thiophenes has been developed. In the presence of triflic acid, 3,4-diaryl thiophenes undergo 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-promoted cyclo-oxidation. NMR and computational studies indicate that protonation of the thiophene plays a key role in this reaction. The reaction can be used to prepare phenanthro[9,10-c]thiophene, as well as derivatives with alkyl, bromo, and methoxy substituents. However, the yields and selectivity of the reaction depend on both the nature and location of the substituents. Bis(3-methoxyphenyl)thiophene reacts under these conditions to give the desired product in 57 % yield, while bis(4-methoxyphenyl)thiophene gives no product. Bis(3-bromophenyl)thiophene did not react, but cyclo-oxidation of bis(4-bromophenyl)thiophene provides the desired product in 34 % yield.

Role of Molecular Recognition in l-Cystine Crystal Growth Inhibition.

l-Cystine kidney stones-aggregates of single crystals of the hexagonal form of l-cystine-afflict more than 20 000 individuals in the United States alone. Current therapies are often ineffective and produce adverse side effects. Recognizing that the growth of l-cystine crystals is a critical step in stone pathogenesis, real-time in situ atomic force microscopy of growth on the (0001) face of l-cystine crystals and measurements of crystal growth anisotropy were performed in the presence of prospective inhibitors drawn from a 31-member library. The most effective molecular imposters for crystal growth inhibition were l-cystine mimics (aka molecular imposters), particularly l-cystine diesters and diamides, for which a kinetic analysis revealed a common inhibition mechanism consistent with Cabrera-Vermilyea step pinning. The amount of inhibitor incorporated by l-cystine crystals, estimated from kinetic data, suggests that imposter binding to the {0001} face is less probable than binding of l-cystine solute molecules, whereas imposter binding to {101̅0} faces is comparable to that of l-cystine molecules. These estimates were corroborated by computational binding energies. Collectively, these findings identify the key structural factors responsible for molecular recognition between molecular imposters and l-cystine crystal kink sites, and the inhibition of crystal growth. The observations are consistent with the reduction of l-cystine stone burden in mouse models by the more effective inhibitors, thereby articulating a strategy for stone prevention based on molecular design.

Regioselective Synthesis of Substituted Cyclopenta[l]phenanthrenes.

A simple and efficient synthesis of cyclopenta[l]phenanthrenes from substituted acetophenones provides access to polycyclic aromatics with a variety of substitution patterns. The synthesis requires only three steps from a silyl enol ether: a Mukaiyama aldol reaction followed by McMurry coupling and then Mallory photocyclooxidation to give the target phenanthrenes. Photocyclization conditions have been found that give regioselective formation of 2,7-phenanthrenes from bis(meta-substituted) stilbenes.